277 results on '"Tolazamide"'
Search Results
2. Incretin-based Drugs and the Risk of Heart Failure
- Author
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Drug Safety and Effectiveness Network, Canada and Canadian Institutes of Health Research (CIHR)
- Published
- 2016
Catalog
3. Incretin-based Drugs and Pancreatic Cancer
- Author
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Drug Safety and Effectiveness Network, Canada and Canadian Institutes of Health Research (CIHR)
- Published
- 2016
4. Antidiabetic Agents
- Author
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LeRoy, Jenna M., Stellpflug, Samuel J., Brent, Jeffrey, editor, Burkhart, Keith, editor, Dargan, Paul, editor, Hatten, Benjamin, editor, Megarbane, Bruno, editor, Palmer, Robert, editor, and White, Julian, editor more...
- Published
- 2017
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- View/download PDF
5. COMPARISON OF DIFFERENT COMPUTATIONAL APPROACHES FOR UNVEILING THE HIGH-PRESSURE BEHAVIOR OF ORGANIC CRYSTALS AT A MOLECULAR LEVEL. CASE STUDY OF TOLAZAMIDE POLYMORPHS.
- Author
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Fedorov, A. Yu. and Rychkov, D. A.
- Subjects
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MOLECULAR crystals , *STACKING interactions , *CASE studies , *BEHAVIOR , *OPTOELECTRONICS - Abstract
The study of the high-pressure behavior of molecular crystals helps find limits of their stability, as well as obtain previously unknown new phases. This may result in the creation of new materials and their forms for a variety of applications: pharmaceutics, optoelectronics, etc. Nevertheless, until recently, there was no practical unified scheme for high-pressure studies of organic molecules, paying close attention to various inter- and intramolecular interactions. In this work, we compare different computational methods for the high-pressure research of molecular crystals in terms of the energy of particular interactions. Tolazamide polymorphs are taken as a representative system. It is shown that not only "structure-forming" interactions, e.g. H-bonds and stacking interactions, but also multiple van der Waals interactions should be taken into account. Moreover, we compare two different concepts for studying particular H-bonds in terms of absolute and relative energies, showing their importance in understanding the high-pressure behavior of tolazamide polymorphs. Finally, several important details about the high-pressure research of organic crystals at a molecular level by computational methods are formulated. [ABSTRACT FROM AUTHOR] more...
- Published
- 2020
- Full Text
- View/download PDF
6. Analysis of Hypoglycemic Drugs by Liquid Chromatography-Tandem Mass Spectrometry.
- Author
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Jannetto PJ and Langman LJ
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- Humans, Chlorpropamide, Tolbutamide, Glipizide, Glyburide, Tolazamide, Rosiglitazone, Pioglitazone, Nateglinide, Chromatography, Liquid, Chromatography, High Pressure Liquid methods, Spectrometry, Mass, Electrospray Ionization methods, Hypoglycemic Agents, Tandem Mass Spectrometry
- Abstract
A rapid and simple method to measure oral hypoglycemic agents is essential in the evaluation of a patient with spontaneous hypoglycemia. As a result, a robust high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the qualitative detection of first-generation sulfonylureas (e.g., chlorpropamide, tolazamide, and tolbutamide), second-generation sulfonylureas (e.g., glimepiride, glipizide, and glyburide), meglitinides (e.g., repaglinide, nateglinide), and thiazolidinediones (e.g., rosiglitazone and pioglitazone). HPLC involved a C8 column and MS/MS was used in electrospray ionization (ESI) positive mode. Identification of all compounds was made using various multiple-reaction monitoring (MRMs). Isotopic labeled chlorpropamide-d4, glimepiride-d5, glyburide-d11, nateglinide-d5, repaglinide-ethyl-d5, rosiglitazone-d3, and zomepirac were used as the internal standards. The cutoffs for each drug were as follows: chlorpropamide 100 ng/mL, tolazamide 50 ng/mL, tolbutamide 20 ng/mL, glimepiride 20 ng/mL, glipizide 5 ng/mL, glyburide 5 ng/mL, repaglinide 5 ng/mL, rosiglitazone 20 ng/mL, pioglitazone 20 ng/mL, and nateglinide 5 ng/mL., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.) more...
- Published
- 2024
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7. To Compare the Effect of a Subcutaneous Canakinumab Administration to Placebo in Patients With Impaired Glucose Tolerance or Patients With Type 2 Diabetes With Differing Baseline Diabetes Therapies
- Author
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External Affairs
- Published
- 2011
8. Characterization of tolazamide binding with glycated and normal human serum albumin by using high-performance affinity chromatography.
- Author
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Tao, Pingyang, Li, Zhao, Woolfork, Ashley G., and Hage, David S.
- Subjects
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ALBUMINS , *GLYCOSYLATED hemoglobin , *SULFONYLUREAS , *TYPE 2 diabetes , *SULFONES - Abstract
Highlights • The binding of tolazamide with albumin was examined using affinity microcolumns. • Normal human serum albumin and glycated forms of this protein were considered. • Frontal analysis was used to examine the overall changes in binding with glycation. • Zonal elution was used to examine binding of this drug at Sudlow sites I and II. • The changes in binding were compared with those seen for other sulfonylurea drugs. Abstract Sulfonylurea drugs are antidiabetic drugs that are utilized in the treatment of type II diabetes and often have significant binding with human serum albumin (HSA). Immobilized samples of normal or glycated HSA in affinity microcolumns were used to investigate interactions of these proteins with the sulfonylurea drug tolazamide. HPLC and frontal analysis were used to first examine the overall binding of this drug with these samples of HSA. It was found that tolazamide had two general classes of binding sites (i.e., high and low affinity) for normal and glycated HSA. The higher affinity sites had binding constants of around 4.3–6.0 × 104 M−1 for these interactions at pH 7.4 and 37 °C, while the lower affinity sites had binding strengths of 4.9–9.1 × 103 M−1. Zonal competition studies between tolazamide and probes for Sudlow sites I and II on HSA were also performed and used to provide site-specific affinities for tolazamide at these sites. A decrease of 22% in affinity was observed for tolazamide at Sudlow site I and an increase up to 58% was seen at Sudlow site II when comparing glycated HSA with normal HSA. These observed changes were compared to those of other first-generation sulfonylurea drugs, providing information on how glycation can alter the total and local binding strength of tolazamide and related compounds with HSA under levels of glycation seen in patients with diabetes. [ABSTRACT FROM AUTHOR] more...
- Published
- 2019
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9. Studies from Federal University Rio Grande do Norte Have Provided New Information about Antidiabetic Agents (Dft Investigation of the Solid-state Properties and Hirshfeld Surface Analysis of Antidiabetic Drugs: Acetohexamide and Tolazamide).
- Abstract
A study conducted at the Federal University Rio Grande do Norte in Natal, Brazil, has investigated the solid-state properties of two antidiabetic drugs, acetohexamide and tolazamide. The researchers used Density Functional Theory (DFT) to study the electronic, optical, and vibrational properties of the crystals, and performed Hirshfeld surface analysis to better understand their crystalline packing. The study found that acetohexamide had an indirect band gap of 2.49 eV, while tolazamide had a direct band gap of 3.25 eV. Both drugs exhibited strong optical absorption in the ultraviolet region. The research also interpreted the IR and Raman spectra of the drugs. This study was supported by Brazilian research agencies CAPES (PNPD), CNPQ, and FAPEAL. [Extracted from the article] more...
- Published
- 2024
10. Folate and Tolazamide: Potential competitive inhibitors of barbiturate by in-silico molecular docking
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Physical fitness ,Tolazamide ,Folic acid ,Health - Abstract
2020 JUL 18 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting based on a preprint abstract, our journalists obtained [...]
- Published
- 2020
11. COMPARISON OF DIFFERENT COMPUTATIONAL APPROACHES FOR UNVEILING THE HIGH-PRESSURE BEHAVIOR OF ORGANIC CRYSTALS AT A MOLECULAR LEVEL. CASE STUDY OF TOLAZAMIDE POLYMORPHS
- Author
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Denis A. Rychkov and A. Yu. Fedorov
- Subjects
Work (thermodynamics) ,Materials science ,Solid-state physics ,Stability (learning theory) ,Stacking ,Tolazamide ,Inorganic Chemistry ,symbols.namesake ,Molecular level ,High pressure ,Materials Chemistry ,medicine ,symbols ,Statistical physics ,Physical and Theoretical Chemistry ,van der Waals force ,medicine.drug - Abstract
The study of the high-pressure behavior of molecular crystals helps find limits of their stability, as well as obtain previously unknown new phases. This may result in the creation of new materials and their forms for a variety of applications: pharmaceutics, optoelectronics, etc. Nevertheless, until recently, there was no practical unified scheme for high-pressure studies of organic molecules, paying close attention to various inter- and intramolecular interactions. In this work, we compare different computational methods for the high-pressure research of molecular crystals in terms of the energy of particular interactions. Tolazamide polymorphs are taken as a representative system. It is shown that not only “structure-forming” interactions, e.g. H-bonds and stacking interactions, but also multiple van der Waals interactions should be taken into account. Moreover, we compare two different concepts for studying particular H-bonds in terms of absolute and relative energies, showing their importance in understanding the high-pressure behavior of tolazamide polymorphs. Finally, several important details about the high-pressure research of organic crystals at a molecular level by computational methods are formulated. more...
- Published
- 2020
- Full Text
- View/download PDF
12. Inhibition Performance of Some Sulfonylurea on Copper Corrosion in Nitric Acid Solution Evaluated Theoretically by DFT Calculations
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Victorien Kouakou, Mougo André Tigori, Paulin Marius Niamien, Amadou Kouyaté, and Albert Trokourey
- Subjects
chemistry.chemical_element ,Tolazamide ,Copper ,chemistry.chemical_compound ,chemistry ,Computational chemistry ,Nitric acid ,medicine ,Molecule ,Reactivity (chemistry) ,Density functional theory ,Erosion corrosion of copper water tubes ,medicine.drug ,Glipizide - Abstract
The theoretical study of chlorpropamide, tolazamide and glipizide was carried out by the Density Functional Theory (DFT) at B3LYP/6-31G(d) level. This study made it possible to determine the global reactivity parameters in order to better understand the interactions between the molecules studied and the copper surface. Then, the determination of local reactivity indices (Fukui functions and dual descriptor) on these molecules resulted in the precision on the most probable centers of nucleophilic and electrophilic attacks within each molecule. The results obtained, show that chloropropamide, tolazamide and glipizide can be good inhibitors against copper corrosion. Thus, the mechanism of copper corrosion inhibition of these compounds in nitric acid solution has been explained by means of theoretical calculations. more...
- Published
- 2020
- Full Text
- View/download PDF
13. Characterization of tolazamide binding with glycated and normal human serum albumin by using high-performance affinity chromatography
- Author
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David S. Hage, Zhao Li, Ashley G. Woolfork, and Pingyang Tao
- Subjects
Glycation End Products, Advanced ,Glycosylation ,medicine.drug_class ,Clinical Biochemistry ,Pharmaceutical Science ,Serum Albumin, Human ,Plasma protein binding ,01 natural sciences ,High-performance liquid chromatography ,Article ,Analytical Chemistry ,Affinity chromatography ,Glycation ,Drug Discovery ,medicine ,Humans ,Hypoglycemic Agents ,Glycated Serum Albumin ,Binding site ,Chromatography, High Pressure Liquid ,Serum Albumin ,Spectroscopy ,Binding Sites ,Chromatography ,010405 organic chemistry ,Chemistry ,010401 analytical chemistry ,Tolazamide ,Human serum albumin ,Sulfonylurea ,0104 chemical sciences ,body regions ,embryonic structures ,Protein Binding ,medicine.drug - Abstract
Sulfonylurea drugs are antidiabetic drugs that are utilized in the treatment of type II diabetes and often have significant binding with human serum albumin (HSA). Immobilized samples of normal or glycated HSA in affinity microcolumns were used to investigate interactions of these proteins with the sulfonylurea drug tolazamide. HPLC and frontal analysis were used to first examine the overall binding of this drug with these samples of HSA. It was found that tolazamide had two general classes of binding sites (i.e., high and low affinity) for normal and glycated HSA. The higher affinity sites had binding constants of around 4.3–6.0 × 104 M−1 for these interactions at pH 7.4 and 37 °C, while the lower affinity sites had binding strengths of 4.9–9.1 × 103 M−1. Zonal competition studies between tolazamide and probes for Sudlow sites I and II on HSA were also performed and used to provide site-specific affinities for tolazamide at these sites. A decrease of 22% in affinity was observed for tolazamide at Sudlow site I and an increase up to 58% was seen at Sudlow site II when comparing glycated HSA with normal HSA. These observed changes were compared to those of other first-generation sulfonylurea drugs, providing information on how glycation can alter the total and local binding strength of tolazamide and related compounds with HSA under levels of glycation seen in patients with diabetes. more...
- Published
- 2019
- Full Text
- View/download PDF
14. Theoretical and experimental investigations on vibrational and structural properties of tolazamide.
- Author
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Karakaya, Mustafa, Sert, Yusuf, Kürekçi, Mehmet, Eskiyurt, Buse, and Çırak, Çağrı
- Subjects
- *
MOLECULAR structure , *VIBRATIONAL spectra , *AB initio quantum chemistry methods , *FOURIER transform infrared spectroscopy , *RAMAN spectra , *SOLID phase extraction , *DENSITY functional theory - Abstract
In this paper, vibrational spectra of tolazamide have been investigated by ab initio techniques in combination with experimental studies. Data on the FT-IR spectra (400–4000 cm −1 ) and Laser-Raman spectra (100–4000 cm −1 ) of tolazamide have been obtained in the solid phase. Assignments corresponding to the vibrational frequencies have been found and interpreted by the contribution of the potential energy distributions. The theoretical results are compared X-ray experimental data for this. Structural parameters such as bond lengths and angles, frequencies and intensities regarding Raman and IR spectra of the compound have been computed by density functional theory and Hartree–Fock methods with 6-311G++( d , p ) and 6-31G( d ) basis sets. They have been observed that the computed vibrational frequencies and optimized structural parameters are consistent with the corresponding experimental results. In addition, the images of frontier molecular orbitals (highest occupied and lowest unoccupied) have been presented and interpreted. [ABSTRACT FROM AUTHOR] more...
- Published
- 2015
- Full Text
- View/download PDF
15. Drug-Polymer Interactions at Water-Crystal Interfaces and Implications for Crystallization Inhibition: Molecular Dynamics Simulations of Amphiphilic Block Copolymer Interactions with Tolazamide Crystals.
- Author
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Gao, Yi and Olsen, Kenneth W.
- Subjects
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DRUG interactions , *INTERFACES (Physical sciences) , *CRYSTALLIZATION , *MOLECULAR dynamics , *AMPHIPHILES , *COPOLYMERS - Abstract
A diblock copolymer, poly(ethylene glycol)-block-poly(lactic acid) ( PEG- b- PLA), modulates the crystal growth of tolazamide ( TLZ), resulting in a crystal morphology change from needles to plates in aqueous media. To understand this crystal surface drug-polymer interaction, we conducted molecular dynamics simulations on crystal surfaces of TLZ in water containing PEG- b- PLA. A 130-ns simulation of the polymer in a large water box was run before initiating 50 ns simulations with each of the crystal surfaces. The simulations demonstrated differentiated drug-polymer interactions that are consistent with experimental studies. Interaction of PEG- b- PLA with the (001) face occurred more rapidly (≤10 ns) and strongly (total interaction energy of −121.1 kJ/mol/monomer) than that with the (010) face (∼35 ns, −85.4 kJ/mol/monomer). There was little interaction with the (100) face. Hydrophobic and van der Waals ( VDW) interactions were the dominant forces, accounting for more than 90% of total interaction energies. It suggests that polymers capable of forming strong hydrophobic and VDW interactions might be more effective in inhibiting crystallization of poorly water-soluble and hydrophobic drugs in aqueous media (such as gastrointestinal fluid) than those with hydrogen-bonding capacities. Such in-depth analysis and understanding facilitate the rational selection of polymers in designing supersaturation-based enabling formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2132-2141, 2015 [ABSTRACT FROM AUTHOR] more...
- Published
- 2015
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16. Tolazamide
- Author
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Abbott, Joel D., Ball, Gene, Boumpas, Dimitrios, Bridges, Stanley Louis, Chatham, Winn, Curtis, Jeffrey, Daniel, Catherine, Hughes, Laura B., Kao, Amy H., Langford, Carol, Lovell, Daniel, Manzi, Susan, Müller-Ladner, Ulf, Patel, Harendra C., Roubey, Robert A. S., Saag, Kenneth, Sabatine, Janice M., Shanahan, Joseph, Simms, Robert, Smith, Edwin, Sundy, John, Szalai, Alexander J., Wimmer, Thomas, and Moreland, Larry W., editor more...
- Published
- 2004
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17. Effect of pressure on two polymorphs of tolazamide: why no interconversion?
- Author
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Boris A. Zakharov, Evgeniy A. Losev, Jernej Stare, Denis A. Rychkov, A. Yu. Fedorov, and Elena V. Boldyreva
- Subjects
Phase transition ,Hydrogen bond ,Solid-state ,Stacking ,Recrystallization (metallurgy) ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Tolazamide ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,Crystallography ,chemistry ,medicine ,General Materials Science ,Methanol ,0210 nano-technology ,Anisotropy ,medicine.drug - Abstract
Two polymorphs of tolazamide, N-[(azepan-1-ylamino)carbonyl]-4-methylbenzenesulfonamide, a sulfonylurea anti-diabetic drug, have different densities and molecular packings. Polymorph II converts into polymorph I in the solid state on heating or via recrystallization if solvent-assisted. The effect of pressure on the two forms and the possibility of a transformation to a denser form on compression have been studied. No phase transitions have been observed in either of the forms in a pentane–isopentane mixture (when no recrystallization is possible). Polymorph II recrystallized partly into a denser polymorph I in methanol at 0.1 GPa, but the transformation stopped at an early stage. Solid state DFT calculations of the two forms as well as conformational landscape investigation in the gas phase were used to rationalize this result. The anisotropic pressure-induced strain of the two polymorphs has been compared in relation to changes in the hydrogen bond geometry and the behavior of stacking interactions. more...
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- 2017
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18. Studies of binding by sulfonylureas with glyoxal- and methylglyoxal-modified albumin by immunoextraction using affinity microcolumns
- Author
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Zuchen Sun, Zhao Li, Elliott Rodriguez, Pingyang Tao, Ryan Matsuda, David S. Hage, and Ashley G. Woolfork
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Glycation End Products, Advanced ,Glycosylation ,Serum Albumin, Human ,Plasma protein binding ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Antibodies ,Chromatography, Affinity ,Article ,Analytical Chemistry ,Glibenclamide ,chemistry.chemical_compound ,Glycation ,Glyburide ,medicine ,Humans ,Drug Interactions ,Gliclazide ,Chromatography ,Protein Stability ,Chemistry ,010401 analytical chemistry ,Organic Chemistry ,Methylglyoxal ,Albumin ,Glyoxal ,General Medicine ,Pyruvaldehyde ,Tolazamide ,Human serum albumin ,0104 chemical sciences ,body regions ,Kinetics ,Sulfonylurea Compounds ,embryonic structures ,Adsorption ,Warfarin ,Protein Binding ,medicine.drug - Abstract
Diabetes is characterized by elevated levels of blood glucose, which can result in the modification of serum proteins. The modification of a protein by glucose, or glycation, can also lead to the formation of advanced glycated end-products (AGEs). One protein that can be modified through glycation and AGE formation is human serum albumin (HSA). In this study, immunoextraction based on polyclonal anti-HSA antibodies was used with high-performance affinity microcolumns to see how AGE-related modifications produced by glyoxal (Go) and methylglyoxal (MGo) affected the binding of HSA to several first- and second-generation sulfonylureas, a class of drugs used to treat type II diabetes and known to bind to HSA. With this approach, it was possible to use a single platform to examine drug interactions with several preparations of HSA. Each applied protein sample could be used over 20–50 experiments, and global affinity constants for most of the examined drugs could be obtained in less than 7.5 min. The binding constants measured for these drugs with normal HSA gave good agreement with global affinities based on the literature. Both Go- and MGo-related modifications at clinically relevant levels were found by this method to create significant changes in the binding by some sulfonylureas with HSA. The global affinities for many of the drugs increased by 1.4-fold or more; gliclazide and tolazamide had no significant change with some preparations of modified HSA, and a small-to-moderate decrease in binding strength was noted for glibenclamide and gliclazide with Go-modified HSA. This approach can be adapted for the study of other drug-protein interactions and alternative modified proteins by altering the antibodies that are employed for immunoextraction and within the affinity microcolumn. more...
- Published
- 2021
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19. Characterization of the rat mesangial cell type 2 sulfonylurea receptor.
- Author
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Asano, Kenichiro, Cortes, Pedro, Garvin, Jeffrey L., Riser, Bruce L., Rodríguez-Barbero, Alicia, Szamosfalvi, Balázs, Yee, Jerry, Asano, K, Cortes, P, Garvin, J L, Riser, B L, Rodríguez-Barbero, A, Szamosfalvi, B, and Yee, J more...
- Subjects
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GENE expression , *EXTRACELLULAR matrix , *CALCIUM metabolism , *POTASSIUM metabolism , *RNA metabolism , *ANIMAL experimentation , *CARRIER proteins , *CELL lines , *COMPARATIVE studies , *DRUG receptors , *DYNAMICS , *HYPOGLYCEMIC sulfonylureas , *KIDNEY glomerulus , *RESEARCH methodology , *MEDICAL cooperation , *POTASSIUM , *RATS , *RESEARCH , *RESEARCH funding , *RNA , *EVALUATION research , *SULFONYLUREAS , *PHARMACODYNAMICS - Abstract
Background: Sulfonylurea receptors are classified as either high-affinity type 1 (SUR1) or low-affinity type 2 receptors (SUR2), and the gene expression of SURs has recently been demonstrated in kidney. However, functional data regarding a renal SUR are lacking. We previously demonstrated that mesangial cell (MC) gene and protein expression of extracellular matrix components were up-regulated by the sulfonylurea, tolazamide. After noting this biological response, we next sought to investigate the presence of a sulfonylurea receptor in rat MCs.Methods: Equilibrium binding studies employing [3H]glibenclamide as a ligand were performed on crude MC membrane preparations. Gene expression for SUR was explored by Northern analysis of cultured MCs and whole kidney tissue. The effect of sulfonylurea on intracellular Ca2+ in MCs was assayed by spectrofluorometry, and glibenclamide-induced changes in the contractility of MCs were assessed.Results: MCs bound [3H]glibenclamide with a KD of 2.6 microM and a Bmax of 30.4 pmol/mg protein as determined by Scatchard analysis. Three SUR2 transcripts were detected in MCs. A major transcript was detected at 5.5 kb and minor transcripts at 7.5 and 8.6 kb. Following sulfonylurea treatment of MCs, real-time videomicroscopy revealed intense MC contraction, coinciding with oscillatory increments of intracellular Ca2+ concentration. Further evidence of sulfonylurea-induced MC contraction was demonstrated by glibenclamide-induced deformation of a silicone rubber substrate.Conclusions: These results demonstrate that SUR2 resides on MCs. Functional activation of this receptor by sulfonylurea induces Ca2+ transients that result in MC contraction. [ABSTRACT FROM AUTHOR] more...- Published
- 1999
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20. The crystal and molecular structure of 1-(Hexahydro-1H-azepin-1-yl)-3-(p-tolylsulfonyl) Urea: Tolazamide (CHNOS).
- Author
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Koo, Chung, Suh, Jung, Yeon, Young, and Watanabe, Tokunosuke
- Abstract
Crystals of tolazamide, CHNOS, are triclinic, space group PĪ, with cell dimensions of a=6.355(2), b=9.223(2), c=13.510(3) A, α=101.04(8), β=92.80(5), γ=85.72(6)° and Z=2. Intensities were collected on an automated four-circle diffractometer using graphite-monochromated Cu K α radiations. The structure was solved by direct method and refined by full-matrix least-squares to an R factor of 0.058 for 1184 observed reflections. The molecules are dimerized by the N-H···O hydrogen bonds. There are only van der Waals interactions between these molecular dimers. [ABSTRACT FROM AUTHOR] more...
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- 1988
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21. Augmentation of the effects of insulin and insulin-like growth factors I and II on glucose uptake in cultured rat skeletal muscle cells by sulfonylureas.
- Author
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Wang, P., Beguinot, F., and Smith, R.
- Abstract
The effect of sulfonylureas on long-term regulation of glucose uptake by insulin and insulin-like growth factors has been studied in the L6 line of cultured skeletal muscle cells. These cells have previously been shown to possess many characteristics of differentiated skeletal muscle and to bind and respond to physiological concentrations of insulin and insulin-like growth factors I and II. Tolazamide (half-maximal at 0.2 mg/ml) augments the effects of insulin, insulin-like growth factor I, and insulin-like growth factor II on glucose uptake, increasing both sensitivity and maximal efficacy of the hormones. In the absence of added hormone, tolazamide has no effect on glucose uptake. A similar increase in insulin-stimulated glucose uptake with unaltered basal uptake occurs with glyburide (half-maximal at 0.5 μg/ml). The action of tolazamide requires long-term exposure to the sulfonylurea (22 h) and is inhibited by cycloheximide, suggesting a process that involves new protein synthesis. In contrast to glucose uptake, amino acid uptake in L6 cells is increased by tolazamide in the absence of hormones. Insulin and the insulin-like growth factors also stimulate amino acid uptake, but this effect is not further augmented by tolazamide. Thus, sulfonylureas appear to directly modulate amino acid uptake, but to indirectly augment glucose uptake through an effect on insulin and insulin-like growth factor stimulated pathways. Neither insulin binding nor insulin degradation is altered by tolazamide, indicating a post-binding mechanism of action. The L6 cultured skeletal muscle cell line should be useful in future studies on the mechanism of the extrapancreatic actions of sulfonylureas. [ABSTRACT FROM AUTHOR] more...
- Published
- 1987
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22. Isoenergetic Polymorphism: The Puzzle of Tolazamide as a Case Study
- Author
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Evgeniy A. Losev, Denis A. Rychkov, Boris A. Zakharov, Yurii V. Seryotkin, Alexander A. Matvienko, Tatiana N. Drebushchak, Sergey G. Arkhipov, Valeri A. Drebushchak, Jernej Stare, Elena V. Boldyreva, and Vasily S. Minkov more...
- Subjects
Crystallography ,Polymorphism (materials science) ,Chemical physics ,Chemistry ,Organic Chemistry ,X-ray crystallography ,medicine ,General Chemistry ,Tolazamide ,Catalysis ,medicine.drug - Abstract
In the present case study of tolazamide we illustrate how many seemingly contradictory results that have been obtained from experimental observations and theoretical calculations can finally start forming a consistent picture: a "puzzle put together". For many years, tolazamide was considered to have no polymorphs. This made this drug substance unique among the large family of sulfonylureas, which was known to be significantly more prone to polymorphism than many other organic compounds. The present work employs a broad and in-depth analysis that includes the use of optical microscopy, single-crystal and powder X-ray diffraction, IR and Raman spectroscopies, DSC, semiempirical PIXEL calculations and DFT of three polymorphs of tolazamide. This case study shows how the polymorphs of a molecular crystal can be overlooked even if discovered serendipitously on one of numerous crystallizations, and how very different molecular packings can be practically isoenergetic but still crystallize quite selectively and transform one into another irreversibly upon heating. more...
- Published
- 2015
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23. Theoretical and experimental investigations on vibrational and structural properties of tolazamide
- Author
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Yusuf Sert, Çağrı Çırak, Mehmet Kürekçi, Mustafa Karakaya, and Buse Eskiyurt
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Chemistry ,Organic Chemistry ,Analytical chemistry ,Hartree–Fock method ,Ab initio ,Tolazamide ,Potential energy ,Molecular physics ,Analytical Chemistry ,Inorganic Chemistry ,Bond length ,symbols.namesake ,medicine ,symbols ,Molecular orbital ,Density functional theory ,Raman spectroscopy ,Spectroscopy ,medicine.drug - Abstract
In this paper, vibrational spectra of tolazamide have been investigated by ab initio techniques in combination with experimental studies. Data on the FT-IR spectra (400–4000 cm−1) and Laser-Raman spectra (100–4000 cm−1) of tolazamide have been obtained in the solid phase. Assignments corresponding to the vibrational frequencies have been found and interpreted by the contribution of the potential energy distributions. The theoretical results are compared X-ray experimental data for this. Structural parameters such as bond lengths and angles, frequencies and intensities regarding Raman and IR spectra of the compound have been computed by density functional theory and Hartree–Fock methods with 6-311G++(d,p) and 6-31G(d) basis sets. They have been observed that the computed vibrational frequencies and optimized structural parameters are consistent with the corresponding experimental results. In addition, the images of frontier molecular orbitals (highest occupied and lowest unoccupied) have been presented and interpreted. more...
- Published
- 2015
- Full Text
- View/download PDF
24. Drug–polymer Interactions at Water–Crystal Interfaces and Implications for Crystallization Inhibition: Molecular Dynamics Simulations of Amphiphilic Block Copolymer Interactions with Tolazamide Crystals
- Author
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Yi Gao and Kenneth W. Olsen
- Subjects
Materials science ,Polymers ,Pharmaceutical Science ,Crystal growth ,Molecular Dynamics Simulation ,Polyethylene Glycols ,law.invention ,Crystal ,Hydrophobic effect ,symbols.namesake ,Molecular dynamics ,law ,Crystallization ,chemistry.chemical_classification ,Tolazamide ,Water ,Hydrogen Bonding ,Interaction energy ,Polymer ,Crystallography ,Solubility ,chemistry ,Lactates ,symbols ,van der Waals force ,Hydrophobic and Hydrophilic Interactions - Abstract
A diblock copolymer, poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA), modulates the crystal growth of tolazamide (TLZ), resulting in a crystal morphology change from needles to plates in aqueous media. To understand this crystal surface drug-polymer interaction, we conducted molecular dynamics simulations on crystal surfaces of TLZ in water containing PEG-b-PLA. A 130-ns simulation of the polymer in a large water box was run before initiating 50 ns simulations with each of the crystal surfaces. The simulations demonstrated differentiated drug-polymer interactions that are consistent with experimental studies. Interaction of PEG-b-PLA with the (001) face occurred more rapidly (≤10 ns) and strongly (total interaction energy of -121.1 kJ/mol/monomer) than that with the (010) face (∼35 ns, -85.4 kJ/mol/monomer). There was little interaction with the (100) face. Hydrophobic and van der Waals (VDW) interactions were the dominant forces, accounting for more than 90% of total interaction energies. It suggests that polymers capable of forming strong hydrophobic and VDW interactions might be more effective in inhibiting crystallization of poorly water-soluble and hydrophobic drugs in aqueous media (such as gastrointestinal fluid) than those with hydrogen-bonding capacities. Such in-depth analysis and understanding facilitate the rational selection of polymers in designing supersaturation-based enabling formulations. more...
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- 2015
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25. Simultaneous Determination of Seven Sulfonylurea-Type Oral Anti-Diabetic Agents in Adulterated Dietary Supplements and Traditional Chinese Medicines by Ultraperformance Liquid Chromatography–Tandem Mass Spectrometry
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Junrong Xi, Lei Zhang, Cunxian Xi, Chun-Yan Zhou, Guo-Min Wang, Bobin Tang, and Zhiqiong Chen
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Detection limit ,Chromatography ,Chemistry ,Formic acid ,Tolazamide ,Mass spectrometry ,Atomic and Molecular Physics, and Optics ,Analytical Chemistry ,Glimepiride ,chemistry.chemical_compound ,Liquid chromatography–mass spectrometry ,medicine ,Gliclazide ,Spectroscopy ,medicine.drug ,Glipizide - Abstract
An ultraperformance liquid chromatography–tandem mass spectrometry method was developed for simultaneous determination of seven sulfonylurea-type oral anti-diabetic agents (glipizide, tolbutamide, tolazamide, gliclazide, glibenclamide, glimepiride, and glurenor) in dietary supplements and traditional Chinese medicines. The samples were extracted twice with methanol by ultrasound. The separation was achieved on a C18 column with the mobile phase consisting of acetonitrile and water (0.2% formic acid (v/v) and 5 mM ammonium acetate), at a flow rate of 0.3 mL/min with gradient elution. The analysis time was 8 min per sample. The proposed method was validated for linearity (r > 0.99), precision (relative standard deviation better than 6.0%), recoveries (83–110%), and the limit of detection in the range 0.3–2 µg kg−1. The proposed method is rapid, reliable, sensitive, accurate, and good applicability, and it was successfully applied to analyze 20 real samples of 15 dietary supplements and five traditional Chin... more...
- Published
- 2014
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26. Similar modes of inclusion in complexes of β-cyclodextrin with sulfonylureahypoglycemic drugs
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Davide Maffeo, Konstantina Yannakopoulou, Anastasia Paulidou, and Irene M. Mavridis
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chemistry.chemical_classification ,Aqueous solution ,Cyclodextrin ,Chemistry ,medicine.drug_class ,Stereochemistry ,General Chemistry ,Condensed Matter Physics ,Tolazamide ,Sulfonylurea ,Bioavailability ,Glimepiride ,Tolbutamide ,medicine ,Moiety ,General Materials Science ,medicine.drug - Abstract
In an attempt to gain insight in the mode of inclusion of sulfonylurea hypoglycemic drugs into β-cyclodextrin (βCD), the molecular structures of the inclusion complexes of three such drugs, tolbutamide (TBM), tolazamide (TLZ) and glimepiride (GLP), have been determined for the first time by X-ray crystallography. The drugs share a common moiety, a H-bond forming sulfonylurea group in the middle, flanked by a tolyl-group at one end and an additional hydrophobic group (different in the three drugs) at the other end, GLP being further elongated by a 2-pyrrolidinone moiety at the tolyl end. The structures of the inclusion complexes comprise βCD dimers aligned in channels. The hydrophobic groups enter the cavities of two adjacent βCD dimers from the primary sides, whereas the hydrophilic sulfonylurea moiety is located in-between, forming H-bonds with the hosts without disturbing the dimers. In the GLP/βCD complex, the pyrrolidinone extension threads the βCD cavity and emerges from the secondary side. These results are supported by NMR 2D ROESY spectra in aqueous solutions. The extended length of GLP imposes a change in the crystal packing placing the βCD dimers further apart. However, the overall inclusion mode of the three drugs is the same, thus a common inclusion and crystallization process is proposed for sulfonylurea drugs. The structures of the complexes explain the effects of complexation on dissolution, bioavailability and hypoglycemic activity. more...
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- 2010
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27. 2-Deoxyglucose Tissue Levels and Insulin Levels Following Tolazamide Dosing in Normal and Obese Mice
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H. P. Fletcher and Carmela A. Skillman
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Male ,Muscle tissue ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Mice, Obese ,Adipose tissue ,Deoxyglucose ,Mice ,Gastrocnemius muscle ,Endocrinology ,Insulin resistance ,Internal medicine ,Deoxy Sugars ,Internal Medicine ,medicine ,Animals ,Insulin ,Tissue Distribution ,Obesity ,business.industry ,Muscles ,Tolazamide ,General Medicine ,medicine.disease ,Sulfonylurea ,medicine.anatomical_structure ,Adipose Tissue ,Insulin Resistance ,business ,medicine.drug - Abstract
The effect of tolazamide (TZ), a sulfonylurea, on 14C-2-deoxyglucose (14C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable yellow mice may be resistant to subchronic treatment with TZ. more...
- Published
- 2009
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28. Fibrinolytic Activity and Haemagglutination Inhibition Immunoassays
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Johs Gormsen and Anne Vad
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Adult ,Liver Cirrhosis ,Male ,Immunodiffusion ,medicine.medical_specialty ,Time Factors ,Cirrhosis ,Plasmin ,Physical Exertion ,Biguanides ,Coronary Disease ,macromolecular substances ,Venous stasis ,In vivo ,Internal medicine ,Humans ,Medicine ,Clofibrate ,Exertion ,Neoplasm Metastasis ,Immunoelectrophoresis ,Aged ,Immunoassay ,Fibrin ,Hemostasis ,Ethylestrenol ,business.industry ,Fibrinolysis ,Nicotinic Acids ,Fibrinogen ,Prostatic Neoplasms ,Tolazamide ,Plasminogen ,Hematology ,Hemagglutination Inhibition Tests ,Middle Aged ,medicine.disease ,Metformin ,Stimulation, Chemical ,Endocrinology ,Immunology ,Female ,business ,medicine.drug ,Hormone - Abstract
Concentrations of fibrinogen-fibrin break-down products (b.d.p.), above 10 ug/ml of serum (+EACA), estimated by haemagglutination inhibition immuno assays, were seldom found in healthy people. In 51 patients with coronary sclerosis and in 31 with other atherosclerotic diseases the amounts were in the lower part of normal range. The mean concentration in 16 patients with metastatic carcinoma was 86.7 and in 16 with hepatic cirrhosis 21.1 ug/ml. 93 patients with other diseases were examined. Huge amounts might be found even when fibrinolytic activity in the blood was very low. Several experiments indicate that b.d.p. also are formed extravascularly and presumably also by other proteases than plasmin. Short-term stimulation of fibrinolytic activity with nicotinic acid (41 patients), venous stasis (35 pts.) and physical exertion (21 pts.), and long-term stimulation with male hormones (5 pts.), metformin (4 pts.), clofibrate (3 pts.), tolazamid (4 pts.) and ethyloestranol + diguanides (11 pts.) was not followed by in vivo increase in b.d.p. more...
- Published
- 2009
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29. Virtual Screening of Natural and Synthetic Ligands Against Diabetic Retinopathy by Molecular Interaction With Angiopoietin-2
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Ashish Chnadra Trivedi, A B Pant, Vikash Thakur, Anshul Tiwari, Prachi Srivastava, and Sandeep Saxena
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Virtual screening ,biology ,business.industry ,Biguanide ,medicine.drug_class ,In silico ,General Medicine ,AutoDock ,Pharmacology ,Tolazamide ,Diabetic Eye Disease ,Receptor tyrosine kinase ,Ophthalmology ,Docking (molecular) ,biology.protein ,Medicine ,business ,medicine.drug - Abstract
Purpose Diabetic retinopathy (DR) is the most common diabetic eye disease and a leading cause of blindness. The role of angiopoietin-2 a tyrosine kinase receptor is well-reported in angiogenesis during the onset of the disease. The purpose of this study is to screen out more potential herbal molecules which can evidently be used as a better, natural and safe herbal drug against this disease. Design In silico virtual screening and molecular interaction studies were performed. Methods The current course of work focused on molecular interactions on angiopoietin-2 protein with selected natural ligands, namely allicin, ajoene, D-pinitol and salacinol, along with synthetic ones like nateglinide, biguanide, tolbutamide and tolazamide. There was an attempt to carry out the virtual comparative study between natural and synthetic ligands. Proceeding toward this approach, docking of all molecules was performed using the Autodock 4.2 program. Results Inference of this interaction study is that D-pinitol, which is the herbal extract of Glycine max, shows a very reliable docking pattern as compared with the synthetic ligand tolazamide. Although the binding energy of a synthetic ligand is lower compared to that of the natural ones, the binding energy of synthetic and natural ligands are at an approximate level. The lower the binding energy, the better the ligand molecular interaction. Conclusions Our findings suggest that D-pinitol, the natural, safe ligand, can be used in the treatment of diabetic retinopathy with few or no side effects after estimating and calculating proper doses using in vitro approaches. more...
- Published
- 2015
30. Determining the Growth Mechanism of Tolazamide by Induction Time Measurement
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Anuj Kuldipkumar, Geoff G. Z. Zhang, and Glen S. Kwon
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Reaction mechanism ,Supersaturation ,Chemistry ,Stereochemistry ,Induction period ,Kinetics ,Nucleation ,Thermodynamics ,General Chemistry ,Condensed Matter Physics ,Tolazamide ,law.invention ,law ,medicine ,General Materials Science ,Growth rate ,Crystallization ,medicine.drug - Abstract
A turbidity measurement-based experimental method for the determination of the crystallization induction period is described. The induction times for crystallization of tolazamide, an oral hypoglycemic agent, were measured over a range of supersaturation in both unseeded and seeded crystallization experiments. The measured induction times were then treated using the expressions developed by van der Leeden et al., which relates the induction time and the supersaturation for various growth mechanisms in unseeded and seeded crystallization. On the basis of these analyses, the growth mechanism of tolazamide was identified as two-dimensional nucleation-mediated growth. The analyses also afforded estimation of the kinetic parameters such as nucleation and growth rate constants. In addition, atomic force microscopy imaging of the major faces of tolazamide crystals corroborated this growth mechanism. more...
- Published
- 2006
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31. Amphiphilic Block Copolymer as a Crystal Habit Modifier
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Yvonne T. F. Tan, Geoff G. Z. Zhang, Mark Goldstein, Yukio Nagasaki, Anuj Kuldipkumar, and Glen S. Kwon
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Crystal growth ,General Chemistry ,Condensed Matter Physics ,Tolazamide ,law.invention ,Crystal ,chemistry.chemical_compound ,chemistry ,law ,Amphiphile ,Copolymer ,medicine ,Organic chemistry ,General Materials Science ,Crystal habit ,Crystallization ,Ethylene glycol ,Nuclear chemistry ,medicine.drug - Abstract
The purpose of this study is to evaluate amphiphilic block copolymers, a new class of additives, for the habit modification of pharmaceuticals. The additive chosen is poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA). The model compound chosen is tolazamide, an oral hypoglycemic pharmaceutical agent. Crystallization was carried out in aqueous media by pH adjustment, with or without additives. PEG-b-PLA was found to be very effective in modifying the crystal habit of tolazamide. The habit changed from a needle shape to a plate shape at a concentration of 12.5 μg/mL. This change in habit required both blocks and could not be achieved in the presence of either block alone. A small amount of copolymer (0.55% weight) was found on/in tolazamide particles crystallized in the presence of 30 μg/mL of copolymer. Washing the crystals with toluene effectively removed the copolymer. It is thus concluded that the block copolymer is mainly adsorbed on the crystal surface(s) rather than being incorporated into the lattice of tolazamide crystals. The recrystallized tolazamide is of the same crystal form as that of the original solid, regardless of the concentration of the copolymer used. more...
- Published
- 2005
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32. A CASE OF SULFONYLUREA INDUCED PHOTOTOXICITY IN AN ELDERLY SUBJECT - A RARE CASE REPORT
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B Patil, Ashok Binjawadgi, Basavambika Anandi, Gayathri A, and Anand R. Kanaki
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Chlorpropamide ,endocrine system ,medicine.medical_specialty ,medicine.drug_class ,business.industry ,nutritional and metabolic diseases ,Hypoglycemia ,medicine.disease ,Tolazamide ,Sulfonylurea ,Dermatology ,Glimepiride ,Endocrinology ,Tolbutamide ,Internal medicine ,medicine ,business ,Pioglitazone ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Glipizide - Abstract
Sulfonylureas are insulin secretagogues used in the management of type 2 diabetes mellitus. The most common side effects are hypoglycemia and weight gain. Less frequent side effects are nausea, vomiting, cholestatic jaundice, agranulocytosis, generalized hypersensitivity reactions which include dermatological reactions. Dermatological reactions of sulfonylurea include photosensitivity. Drug induced photosensitivity is one of the important adverse drug reaction. Hence we would like to present here a case of sulfonylurea induced photosensitivity in an elderly diabetic male. He presented with rashes, itching, and intolerance to light and eruptions with exfoliation of skin over the sun exposed parts of the body. INTRODUCTION: Sulfonylureas are insulin secretagogues used in type 2 diabetes mellitus. They are substituted aryl sulfonylureas. They differ by substitutions at the para position on the benzene ring and at one nitrogen residue of the urea moiety. The sulfonylureas are divided into two generations. The first generation sulfonylureas (tolbutamide, tolazamide and chlorpropamide) are rarely used now. The second generation sulfonylureas are more potent and include glimepiride, glipizide and glyburide. Main side effects of sulfonylureas are hypoglycemia and weight gain. Other less common side effects are nausea, vomiting, cholestatic jaundice, agranulocytosis, generalized hypersensitivity reactions which include dermatological reactions like photosensitivity1. Photosensitivity is one of the neglected side effects of sulfonylureas and here we present a rare case of sulfonylurea induced photosensitivity. CASE REPORT: A 60 year old male patient presented with rashes, itching, and intolerance to light with exfoliation of skin over the sun exposed parts of the body. He had developed phobia for exposure to light and avoided taking pictures with camera flash. He was known diabetic on treatment with tablet glyburide 5mg (sulfonylurea) and metformin 500mg twice daily since 2 years. The patient was treated with sunscreen lotion for his skin lesions, but showed no improvement even after 2 months. Later, upon review of his drug history, it was revealed that glyburide (sulfonylurea) caused phototoxicity, and was withdrawn. The patient was put on an alternate hypoglycemic drug combination of pioglitazone 15mg and metformin 500mg twice daily. He also continued sunscreen application and sun protection. He improved gradually within 15 days and this suggests that it is a case of sulfonylurea induced phototoxicity. more...
- Published
- 2013
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33. Detection of anti-diabetics in equine plasma and urine by liquid chromatography?tandem mass spectrometry
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Kenneth C.H. Yiu, Keith L. Watkins, Terence S.M. Wan, Brian D. Stewart, and Emmie N.M. Ho
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Spectrometry, Mass, Electrospray Ionization ,Chromatography ,Swine ,Chemistry ,Clinical Biochemistry ,Reproducibility of Results ,Cell Biology ,General Medicine ,Urine ,Nateglinide ,Tolazamide ,Sensitivity and Specificity ,Biochemistry ,Analytical Chemistry ,Matrix (chemical analysis) ,Glimepiride ,Liquid chromatography–mass spectrometry ,medicine ,Animals ,Hypoglycemic Agents ,Gliclazide ,Chromatography, High Pressure Liquid ,medicine.drug ,Glipizide - Abstract
Aim: Anti-diabetics such as sulfonylurea and thiazolidinedione derivatives are hypoglycemic drugs used for the treatment of diabetes. However, they can also be used as a stopper in horseracing. This paper describes a convenient method for the separation and simultaneous detection of 10 anti-diabetic drugs (namely glipizide, glibenclamide, glimepiride, gliclazide, tolazamide, tolbutamide, nateglinide, repaglinide, rosiglitazone and pioglitazone) in equine plasma and urine by LC–MS-MS. Method: The anti-diabetics were isolated from equine plasma and urine by liquid–liquid extraction with 1,2-dichloroethane at acidic pH, and analysed by LC–MS-MS in the positive electrospray ionisation mode. Separation of 10 anti-diabetic drugs was achieved with a reversed phase C8 column using a mixture of aqueous ammonium formate (pH 3.0, 10 mM) and methanol as the mobile phase. Results: Detection and confirmation of the 10 anti-diabetic drugs at 10 ng/mL each in equine plasma and equine urine were achieved by full-scan MS-MS. All of these drugs were detected consistently at this concentration in spiked samples of different plasma and urine ( n = 15 each). No significant matrix interferences were observed at the expected retention times of the targeted ions in blank urine samples ( n = 30). This method has been used successfully in the analysis of drug-administration samples as well as official racing samples. Conclusion: An LC–MS-MS method has been developed for the simultaneous detection of 10 anti-diabetics in equine plasma and urine. This method can be used to detect the abuse of anti-diabetic drugs in racehorses. more...
- Published
- 2004
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34. Efficacy of Sulfonylureas with Insulin in Type 2 Diabetes Mellitus
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Udaya M Kabadi and Mary U. Kabadi
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Type 2 diabetes ,030204 cardiovascular system & hematology ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Insulin ,Pharmacology (medical) ,Glycemic ,business.industry ,Body Weight ,Type 2 Diabetes Mellitus ,Middle Aged ,medicine.disease ,Tolazamide ,Glimepiride ,Sulfonylurea Compounds ,Endocrinology ,Diabetes Mellitus, Type 2 ,Regular insulin ,Drug Therapy, Combination ,Female ,business ,medicine.drug ,Glipizide - Abstract
BACKGROUND: In subjects with type 2 diabetes mellitus, glycemic control deteroriates while patients use sulfonylurea drugs during the course of the disease. Adjunctive therapy with insulin at this stage requires a lesser daily insulin dose in comparison with insulin monotherapy while restoring desirable glycemic control. However, data regarding direct comparison between various sulfonylureas in this regard are lacking. OBJECTIVE: To examine comparative efficacies of adjunctive therapy with insulin in subjects with type 2 diabetes manifesting lapse of glycemic control while receiving various individual sulfonylurea drugs. METHODS: Four groups of 10 subjects, each presenting with glycosylated hemoglobin (HbA1C) >8.0% while using either tolazamide, glyburide, glipizide Gastrointestinal Therapeutic System (GITS), or glimepiride, were recruited. Two from each group were randomized to receive placebo; the others continued the same drug. Pre-supper subcutaneous 70 NPH/30 regular insulin was initiated at 10 units and gradually increased and adjusted as necessary to attain fasting blood glucose levels between 80 and 120 mg/dL and maintain the same range for 6 months. Fasting plasma glucose, plasma C-peptide, and HbA1C concentrations were determined prior to the addition of insulin and at the end of the study. Daily insulin dose and changes in body weight (BW) were noted at the end of the study, and the number of hypoglycemic events during the last 4 weeks of the study was determined. RESULTS: Daily insulin dose (units/kg BW), weight gain, and number of hypoglycemic events were significantly lower (p < 0.01) in subjects receiving sulfonylureas in comparison with placebo. However, the daily insulin dose alone was significantly lower (p < 0.05) with glimepiride (0.49 ± 0.10; mean ± SE) than with other sulfonylureas (tolazamide 0.58 ± 0.12, glyburide 0.59 ± 0.12, glipizide GITS 0.59 ± 0.14). Finally, a significant correlation (r = 0.68; p < 0.001) was noted between suppression of plasma C-peptide level and the daily insulin dose among all participants. CONCLUSIONS: By lowering the daily insulin dose, sulfonylurea drugs appear to improve the sensitivity of exogenous insulin in subjects with type 2 diabetes mellitus manifesting lapse of glycemic control. Moreover, glimepiride appears to possess a greater insulin-sparing property than other sulfonylureas. more...
- Published
- 2003
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35. Screening, library-assisted identification and validated quantification of oral antidiabetics of the sulfonylurea-type in plasma by atmospheric pressure chemical ionization liquid chromatography–mass spectrometry
- Author
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Frank T. Peters, Armin A. Weber, Hans H. Maurer, Carsten Kratzsch, and Thomas Kraemer
- Subjects
Clinical Biochemistry ,Administration, Oral ,Atmospheric-pressure chemical ionization ,Mass spectrometry ,Sensitivity and Specificity ,Biochemistry ,Mass Spectrometry ,Analytical Chemistry ,Glibornuride ,chemistry.chemical_compound ,Liquid chromatography–mass spectrometry ,medicine ,Humans ,Hypoglycemic Agents ,Chemical ionization ,Chromatography ,Reproducibility of Results ,Cell Biology ,General Medicine ,Reference Standards ,Tolazamide ,Glimepiride ,Atmospheric Pressure ,Sulfonylurea Compounds ,chemistry ,Gliquidone ,Chromatography, Liquid ,medicine.drug - Abstract
An atmospheric pressure chemical ionization liquid chromatographic-mass spectrometric (APCI-LC-MS) LC-MS assay is presented for fast and reliable screening and identification as well as precise and sensitive quantification of oral antidiabetics of the sulfonylurea-type (OADs) in plasma. It allowed the specific diagnosis of an overdose situation or a Munchausen syndrome caused by ingestion of OADs. After liquid-liquid extraction, the OADs glibenclamide, glibornuride, gliclazide, glimepiride, glipizide, gliquidone, glisoxepide, tolazamide and tolbutamide were separated using fast gradient elution. After screening and identification in the scan mode using our new LC-MS library, the OADs were quantified in the selected-ion mode. The quantification assay was validated according to the criteria established by the Journal of Chromatography B. All validation data were inside the required limits. The assay is part of a general LC-MS procedure for fast screening, identification and quantification of different toxicologically relevant compounds in plasma and has proven to be appropriate for OADs. more...
- Published
- 2002
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36. Evaluation of a novel non-porous membrane extraction probe to determine sulphonylureas in plasma with analysis by LC-MS/MS
- Author
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Frank G. P. Mullins
- Subjects
Chlorpropamide ,Chromatography ,Chemistry ,Filtration and Separation ,Reversed-phase chromatography ,Tolazamide ,High-performance liquid chromatography ,Analytical Chemistry ,medicine ,Gliclazide ,Sample preparation ,Quantitative analysis (chemistry) ,medicine.drug ,Blood sampling - Abstract
A silicone rubber thin membrane extraction probe was developed and evaluated as a sample preparation device prior to LC-MS/MS analysis. The permeation properties of the membrane were evaluated using the five selected sulphonylureas, tolbutamide, gliclazide, chlorpropamide, tolazamide, and glibenclamide. The effects of pH, temperature, and immersion time were investigated. A method for the determination of gliclazide in plasma was validated over the concentration range of 0.10-9.85 μg/mL covering the anticipated in-vivo concentrations. The applicability of the method was demonstrated by the determination of plasma concentrations of gliclazide in a human volunteer following an 80 mg oral dose of gliclazide with blood sampling out to 48 hours. more...
- Published
- 2001
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37. Effects of oral antihyperglycemic agents on extracellular matrix synthesis by mesangial cells
- Author
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Bruce L. Riser, Alicia Rodríguez-Barbero, Kenichiro Asano, Pedro Cortes, Jerry Yee, and Robert G. Narins
- Subjects
TGF-β ,medicine.medical_specialty ,collagen metabolism ,Monosaccharide Transport Proteins ,Glucose uptake ,Administration, Oral ,030209 endocrinology & metabolism ,Deoxyglucose ,03 medical and health sciences ,0302 clinical medicine ,Transforming Growth Factor beta ,Culture Techniques ,Internal medicine ,medicine ,Animals ,Hypoglycemic Agents ,sulfonylureas ,RNA, Messenger ,030304 developmental biology ,Glucose Transporter Type 1 ,0303 health sciences ,biology ,Mesangial cell ,diabetic nephropathy ,Glucose transporter ,Tolazamide ,Biological Transport ,Metabolism ,Rats, Inbred F344 ,Extracellular Matrix ,Glomerular Mesangium ,Rats ,Fibronectin ,Endocrinology ,Nephrology ,biology.protein ,GLUT1 ,metformin ,glomerulosclerosis ,medicine.drug - Abstract
Effects of oral antihyperglycemic agents on extracellular matrix synthesis by mesangial cells. Background Increased expression of the glucose transporter GLUT1 in mesangial cells (MCs) markedly stimulates glucose transport and the formation of extracellular matrix (ECM), even when ambient glucose concentrations are low. Certain antihyperglycemic agents cause GLUT1 overexpression and increase glucose transport in various tissues. However, their effects on the kidney are unknown. Because diabetic glomerulosclerosis is characterized by the accumulation of mesangial matrix, we studied the effects of antihyperglycemic agents on matrix metabolism in MCs cultured either in 8 or 20mm glucose. Methods Membrane-associated GLUT1 was measured by immunoblotting. The initial rate of glucose transport was determined according to the 2-deoxy-D[ 14 C(U)]glucose uptake. Collagen metabolism was studied by metabolic radiolabeling with [ 14 C]-proline. Fibronectin in the medium was measured by ELISA. GLUT1 mRNA was estimated by Northern analysis. Results The sulfonylurea tolazamide increased GLUT1 protein expression by 107 and 69% in 8 and 20mm glucose-grown cells, respectively. However, GLUT1 mRNA levels remained unchanged. Transporter-dependent deoxyglucose uptake was increased by tolazamide up to 184% in a dose-dependent fashion and was evident at both glucose concentrations after three or five days of exposure to the drug. Tolazamide significantly stimulated transforming growth factor-β1 (TGF-β1) secretion and the total synthesis of collagen and collagen and fibronectin accumulation in the medium of MCs maintained in high or low glucose concentrations. The biguanide metformin did not alter GLUT1 expression, glucose transport, fibronectin formation, or collagen metabolism, except at high concentrations. Conclusion Tolazamide markedly enhances ECM synthesis and accumulation in MCs probably by stimulating GLUT1 expression, glucose transport and TGF-β1 secretion, irrespective of the ambient glucose concentration. This effect was dose-dependent and minimally inducible by metformin. more...
- Published
- 1998
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38. Heterogeneity of the inhibitory influence of sulfonylureas on prostanoid-induced smooth muscle contraction
- Author
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Johan Van de Voorde and Christophe Delaey
- Subjects
Male ,medicine.medical_specialty ,Vascular smooth muscle ,Guinea Pigs ,Aorta, Thoracic ,Bronchi ,In Vitro Techniques ,Biology ,Muscle, Smooth, Vascular ,Glibenclamide ,Tolbutamide ,Species Specificity ,Internal medicine ,Glyburide ,medicine ,Animals ,Humans ,Hypoglycemic Agents ,Drug Interactions ,Rats, Wistar ,Pharmacology ,Tolazamide ,Muscle, Smooth ,Arteries ,Smooth muscle contraction ,Interlobar arteries ,Rats ,Trachea ,Endocrinology ,medicine.anatomical_structure ,Gliclazide ,Prostaglandins ,Cattle ,Female ,medicine.symptom ,Vasoconstriction ,Muscle Contraction ,medicine.drug ,Muscle contraction - Abstract
In addition to their hypoglycemic influence, sulfonylureas have been reported to inhibit prostanoid-induced vasoconstriction. Using isometric tension measurements we investigated whether this inhibitory influence is exerted by different sulfonylureas in various types of blood vessels from different species and in other types of smooth muscle cells. It was found that in addition to glibenclamide and tolbutamide also gliclazide (1 mM) and tolazamide (1 mM) block contractions induced by prostaglandin F2α and the thromboxane A2 mimetic U-46619 in rat aorta, but not the contractions elicited by norepinephrine, serotonin or high potassium. Glibenclamide (10 μM) inhibits the prostaglandin F2α- and U-46619-induced contractions on rat tail, femoral and renal interlobar arteries and on bovine retinal and ciliary arteries, but not those on aorta and carotid artery from guinea pigs and on human subcutaneous arteries. Glibenclamide (10 μM), tolbutamide (1 mM), tolazamide (1 mM) and gliclazide (1 mM) all block contractions induced by U-46619, but not those induced by carbachol, on rat intrapulmonary bronchioles. However, prostanoid-induced contractions of guinea-pig trachea and main bronchi are not influenced by glibenclamide (10 μM). From these results it is concluded that the ability of sulfonylureas to block prostanoid-induced contractions is shared by all sulfonylureas tested, that this is not limited to vascular smooth muscle cells and that it shows a heterogeneity, that might be linked to interspecies differences. © 1997 Elsevier Science B.V. more...
- Published
- 1997
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39. Phototoxicity to sulphonamide-derived oral antidiabetics and diuretics: investigations in hairless mice
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E. Selvaag and Per Thune
- Subjects
Trichlormethiazide ,Time Factors ,Ultraviolet Rays ,Tolbutamide ,medicine.medical_treatment ,Immunology ,Occlusive Dressings ,Dermatology ,Pharmacology ,Benzothiadiazines ,Mice ,Necrosis ,Furosemide ,Glyburide ,medicine ,Animals ,Edema ,Hydroflumethiazide ,Hypoglycemic Agents ,Immunology and Allergy ,Radiology, Nuclear Medicine and imaging ,Bendroflumethiazide ,Colloids ,Photosensitivity Disorders ,Diuretics ,Bumetanide ,Mice, Hairless ,Mice, Inbred C3H ,Sulfonamides ,Chemistry ,Tolazamide ,General Medicine ,Intradermal Tests ,Disease Models, Animal ,Hydrochlorothiazide ,Solvents ,Female ,Diuretic ,Phototoxicity ,Glipizide ,Bandages, Hydrocolloid ,medicine.drug - Abstract
The oral antidiabetics glibenclamide, glipizide, glymidine, tolazamide and tolbutamide and the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, furosemide, hydrochlorothiazide, hydroflumethiazide and trichlormethiazide were investigated for phototoxic effects in hairless mice. The back of the animals (hr/hr-c3H/TifBom) was covered with Duoderm dressing, and at the site of two punched out holes 0.05 ml of the test substances at 0.25 mol/1 concentration and the solvent alone as control were injected intradermally, respectively. Both test and control sites were irradiated with 6–12 J/cm2 of longwave UVA light from a “Bluelight 2000” apparatus (Honle, Martinsried, Germany). Skin reactions were read at 24 and 48 h. Compared to the solvent alone, all of the test substances induced reactions (necrosis or oedema) - most frequently seen by macroscopic and histologic investigation and by measurements with a thickness gage. Injection of the test substance or solvent alone without or with subsequent UVA irradiation, as well as UVA alone, did not induce measurable skin changes in this model. Three oral antidiabetics and four diuretics, not yet described to induce photosensitivity in vitro nor in vivo, were detected as potential photosensitizers using our animal model. more...
- Published
- 1997
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40. Photohemolysis Due to Oral Antidiabetic Drugs
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Edgar Selvaag
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Chlorpropamide ,Chemistry ,Health, Toxicology and Mutagenesis ,Pharmacology ,Toxicology ,Tolazamide ,Glibornuride ,Ophthalmology ,Carbutamide ,chemistry.chemical_compound ,Tolbutamide ,medicine ,Gliclazide ,Gliquidone ,medicine.drug ,Glipizide - Abstract
The oral hypoglycemic sulfonamides carbutamide, chlorpropamide, glibenclamide, glibornuride, gliclazide, glipizide, gliquidone, glisoxepide, glymidine, tolazamide, and tolbutamide were investigated for photohemolytic properties in vitro. Irradiation with a solar simulator revealed hemolysis in the presence of chlorpropamide, glipizide, gliquidone, glymidine, and tolbutamide (all at a concentration of 10−3 mol/L). Except for glymidine, which exerted photohemolysis at the concentration 10−4 mol/L, no hemolytic effects were seen in the concentration of 10−4 mol/L or 10−5 mol/L. Irradiation with light sources emitting mainly ultraviolet B (UVB), ultraviolet A (UVA), or visible light did not induce phototoxic hemolysis with any of the test substances. Tolbutamide and chlorpropamide have previously been described as a cause of clinical photosensitivity, whereas the other drugs so far have not shown phototoxic effects in humans. more...
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- 1997
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41. Preparation and in Vitro Dissolution Profiles of Tolazamide-Polyethylene Glycol Solid Dispersions
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S. R. Dipali and G. V. Betageri
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Pharmacology ,Materials science ,In vitro dissolution ,Organic Chemistry ,Significant difference ,Pharmaceutical Science ,Polyethylene glycol ,Tolazamide ,Dosage form ,Solvent ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,Drug Discovery ,PEG ratio ,medicine ,Organic chemistry ,Dissolution ,medicine.drug - Abstract
The objective of this study is to prepare solid dispersions of tolazamide (TLZ) using polyethylene glycol (PEG) and measure the dissolution of TLZ. PEG 8000 was used as carrier to prepare solid dispersions by melt and solvent methods. Dissolution studies indicated a remarkable increase in the rate of dissolution of TLZ when dispersed in PEG as well as with physical mixture of TLZ and PEG. The rate of dissolution of TLZ was faster with solid dispersions containing TLZ:PEG (1:5) and (1:10) compared to physical mixtures and pure TLZ. The effect of buffer on dissolution was studied. In general the dissolution of TLZ was less in phosphate buffered saline (PBS, pH 7.4) compared to Tris buffer. However, there was no significant difference in the extent of dissolution of TLZ from solid dispersions and physical mixture compared to pure TLZ. Solid dispersions prepared by solvent method showed faster dissolution rates compared to melt method. These results suggest that the rate of dissolution can be increase... more...
- Published
- 1995
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42. Spectrophotometric Determination of Some Pharmaceutical Compounds Using 2,2-Diphenyl-1-picrylhydrazyl
- Author
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Kamla M. Emara, Abdel-Maboud I. Mohamed, Hassan F. Askal, and Ibrahim A. Darwish
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chemistry.chemical_classification ,Isocarboxazid ,Chromatography ,medicine.diagnostic_test ,DPPH ,Biochemistry (medical) ,Clinical Biochemistry ,Inorganic chemistry ,Tolazamide ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Iproniazid ,chemistry ,Spectrophotometry ,Reagent ,Electrochemistry ,medicine ,Thiol ,Gliclazide ,Spectroscopy ,medicine.drug - Abstract
A spectrophotometric method for the determination of some pharmaceutical amides, hydrazides and thiols is described. The method is based on the reaction of the studied drugs with 2,2-diphenyl-1-picryl hydrazyl (DPPH). The latter is employed to abstract a hydrogen atom from the drugs thereby promoting a process of radical coupling. This results in a reduction of the violet colour of DPPH with the formation of the yellow coloured 2,2-diphenyl-1-picrylhydrazine (DPPH2). This fading in colour of DPPH reagent depends on the concentration of the drug being determined. Beer's law is obeyed in the ranges of 1–5 μg/ml (for isocarboxazid and gliclazide), 0.25–2.5 μg/ml (for isoniazid), 0.5–5 μg/ml (for iproniazid), 1–7 μg/ml (for tolazamide), 2–15 μg/ml (for captopril) and 1–6 μg/ml (for sulphathiourea). The validity of the method was tested by analysing the studied drugs in pure form as well as in tablets. Results of analyses were compared statistically with the official or reported methods. more...
- Published
- 1993
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43. Is Combination Sulfonylurea and Insulin Therapy Useful in NIDDM Patients?: A metaanalysis
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Michael R. Tuley, Gilbert Ramirez, Jacqueline A. Pugh, Samuel J Friedberg, John Sawyer, and Mary L Wagner
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Blood Glucose ,Chlorpropamide ,medicine.medical_specialty ,Combination therapy ,medicine.drug_class ,MEDLINE ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Population ,law.invention ,Meta-Analysis as Topic ,Randomized controlled trial ,law ,Diabetes mellitus ,Internal medicine ,Glyburide ,Internal Medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Medicine ,education ,Glycemic ,Glycated Hemoglobin ,Advanced and Specialized Nursing ,education.field_of_study ,C-Peptide ,business.industry ,Tolazamide ,Middle Aged ,medicine.disease ,Sulfonylurea ,United States ,Sulfonylurea Compounds ,Treatment Outcome ,Endocrinology ,Diabetes Mellitus, Type 2 ,Gliclazide ,Meta-analysis ,Drug Therapy, Combination ,Periodicals as Topic ,business - Abstract
OBJECTIVE To assess the efficacy of combination therapy with insulin and sulfonylurea in the treatment of NIDDM. RESEARCH DESIGN AND METHODS Studies published between January 1966 and January 1991 were identified through a computerized Medline search and by hand searching the bibliographies of identified articles. We identified 17 eligible randomized, controlled trials of combination therapy in NIDDM. These trials had a minimum duration of 8 wk and at least one of three outcome measures (fasting glucose, HbA1, or C-peptide) with SD or SE of the mean reported to do metaanalysis. With standardized forms, three independent reviews abstracted measures of study quality and specific descriptive information about population, intervention, and outcome measurements. RESULTS We calculated effect size and weighted mean changes of the three outcome measures for control and treatment groups. In the treatment group, the fasting plasma glucose decreased from a mean of 11.4 mM (206 mg/dl) at baseline to a mean of 9.16 mM (165 mg/dl) posttreatment, whereas the control group decreased from (11.3 to 10.8 mM) (204 to 194 mg/dl) (effect size 0.39, P < 0.0001). For HbA1, the treatment group decreased from a baseline of 11.0 to 10.2% compared to 11.0 and 11.2% in the control group (effect size 0.43, P < 0.0001). For fasting C-peptide, the treatment group increased from 0.49 to 0.58 nM (1.45 to 1.75 ng/ml) compared with 0.47 and 0.43 (1.42 and 1.30) for the control group (effect size 0.26, P < 0.017). CONCLUSION Combined insulin-sulfonylurea therapy leads to modest improvement in glycemic control compared with insulin therapy alone. With combined therapy, lower insulin doses may be used to achieve similar control. Obese patients with higher fasting C-peptides may be more likely to respond than others. more...
- Published
- 1992
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44. Spectrophotometric determination of some pharmaceutical amides through charge—transfer complexation reactions
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Hassan F. Askal and Gamal A. Saleh
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Morphazinamide ,Hydrochloride ,Clinical Biochemistry ,Pharmaceutical Science ,chemistry.chemical_element ,Iodine ,Dosage form ,Analytical Chemistry ,symbols.namesake ,chemistry.chemical_compound ,Spectrophotometry ,Drug Discovery ,medicine ,Diphenylacetic Acids ,Spectroscopy ,Chromatography ,medicine.diagnostic_test ,Tolazamide ,Amides ,Trimethobenzamide Hydrochloride ,Gibbs free energy ,Quaternary Ammonium Compounds ,Solutions ,chemistry ,Pyrazines ,Benzamides ,symbols ,Indicators and Reagents ,Spectrophotometry, Ultraviolet ,Absorption (chemistry) ,Tablets ,medicine.drug ,Nuclear chemistry - Abstract
A spectrophotometric method is described for the assay of fenpipramide hydrochloride, isopropamide iodide, trimethobenzamide hydrochloride, morphazinamide hydrochloride and tolazamide. The method is based on the formation of a charge—transfer complex between the drug as n -donor and iodine, a ∂-acceptor. The product exhibits absorption maxima at 295 and 365 nm; measurements are made at 365 nm for fenpipramide and at 295 nm for the other compounds. Beer's law is obeyed in a concentration range of 1–120 μg ml −1 . The method is rapid, simple and sensitive and can be applied to the analysis of some commercial and laboratory prepared tablets without interference. A more detailed investigation of the complex was made with respect to its composition. association constant and free energy change. more...
- Published
- 1991
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45. Use of Sulfonylurea Agents in Older Diabetic Patients
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Mayer B. Davidson and Anne L. Peters
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Chlorpropamide ,medicine.medical_specialty ,Pediatrics ,business.industry ,medicine.drug_class ,Insulin ,medicine.medical_treatment ,Hypoglycemia ,Tolazamide ,medicine.disease ,Sulfonylurea ,Surgery ,Acetohexamide ,Diabetes management ,Diabetes mellitus ,medicine ,Geriatrics and Gerontology ,business ,medicine.drug - Abstract
The elderly patient with type II diabetes should be treated in much the same fashion as a younger person with the same disease, although emphasis needs to be placed on minimizing side effects, drug interactions, and hypoglycemia. Chlorpropamide should not be used in these patients, unless there is no other choice. The remaining agents--tolbutamide, acetohexamide, tolazamide, glyburide, and glipizide--should be started at low doses and gradually increased until optimal diabetic control is reached. The initial treatment goal is a FPG level of less than 180 mg/dl and a final goal is a 1- to 2-hour PPG concentration between 140 and 180 mg/dl. The glycosylated hemoglobin value should be no greater than 1.5% above the upper limit of normal, and should be lower, if possible. It must be kept in mind, however, that the closer diabetic patients are to achieving euglycemia, the more likely is hypoglycemia. Treatment goals therefore may have to be relaxed in someone at increased risk of hypoglycemia (e.g., patients with irregular eating habits or renal insufficiency) or when hypoglycemia may pose a greater hazard (e.g., patients with coronary artery or cerebral vascular disease). Patients on sulfonylurea agents should have blood glucose values measured once a month and glycosylated hemoglobin levels determined once every 3 months to alert the clinician to the possible need to adjust therapy. In this way, potential hypoglycemia can be avoided if blood glucose levels are drifting too low and chronic hyperglycemia can be identified and treated within a short period of time. When a patient's status changes--e.g., he is placed on new medication, becomes depressed and anorexic, or develops another medical problem--care must be taken to re-evaluate his diabetes management. Drugs such as sulfonamide antibiotics can potentiate the action of the sulfonylureas and cause hypoglycemia, renal insufficiency may necessitate changing the type of sulfonylurea agent or decreasing the dose, and malnutrition may obviate any need for therapy with an oral hypoglycemic agent. If these guidelines are kept in mind, the older diabetic patient can be managed on a sulfonylurea agent in conjunction with the appropriate diet. Should these measures prove to be ineffective, then insulin therapy should be instituted. Controlling chronic hyperglycemia will help improve the quality of life for patients with diabetes and decrease the probability of developing some of the devastating complications associated with this disease. more...
- Published
- 1990
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46. Adjunctive Use of Tolazamide in Newly-Diagnosed Diabetic Children
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Paula Stoler, Beverly Faro, R. Sanders, Kenneth McCormick, and Gail Mick
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Blood Glucose ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Placebo ,Biochemistry ,law.invention ,Endocrinology ,Pharmacotherapy ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Insulin ,Prospective Studies ,Child ,Prospective cohort study ,Glycated Hemoglobin ,C-Peptide ,business.industry ,Biochemistry (medical) ,Tolazamide ,General Medicine ,medicine.disease ,Clinical trial ,Diabetes Mellitus, Type 1 ,Child, Preschool ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
Recent data suggests that one of the major actions of sulfonylureas is to potentiate the anabolic cellular effects of insulin. This is the first study to examine the use of sulfonylureas as adjunctive therapy in newly-diagnosed type I diabetic children. A random, prospective, double blind study over 15 months, stratified by age at diagnosis, was conducted. The treatment group (n = 13) received daily oral weight-adjusted tolazamide whereas the control group (n = 11) received placebo. Monthly comparison of the HbA1 values between groups revealed no statistical difference; likewise, the fasting serum C-peptide values were not dissimilar. The mean daily insulin dose per kilogram, however, was less in the tolazamide group (P less than 0.001). The data suggests that the addition of tolazamide may not be of therapeutic benefit in newly diagnosed juvenile diabetics, although insulin requirements may be reduced. more...
- Published
- 1990
- Full Text
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47. Effect of Sulfonylureas Administered Centrally on the Blood Glucose Level in Immobilization Stress Model
- Author
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Su-Min Lim, Jae-Seung Hong, Yun-Beom Sim, Naveen Sharma, Jun-Sub Jung, Soo-Hyun Park, Sung-Su Kim, and Hong-Won Suh
- Subjects
Immobilization stress ,medicine.medical_specialty ,Physiology ,medicine.drug_class ,medicine.medical_treatment ,chemistry.chemical_compound ,Plasma insulin level ,Sulfonylurea ,Corticosterone ,Internal medicine ,medicine ,Blood glucose ,Pharmacology ,business.industry ,Insulin ,Brain ,Tolazamide ,Glimepiride ,Endocrinology ,chemistry ,Original Article ,business ,Icr mice ,medicine.drug ,Glipizide - Abstract
Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 µg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level. more...
- Published
- 2015
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48. Insulin and Synthetic Hypoglycemic Agents
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V.J. Hruby and R.S. Vardanyan
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Chlorpropamide ,medicine.medical_specialty ,business.industry ,Insulin ,medicine.medical_treatment ,Blood sugar ,Tolazamide ,medicine.disease ,Endocrinology ,Tolbutamide ,Acetohexamide ,Internal medicine ,Diabetes mellitus ,medicine ,business ,Pancreatic hormone ,medicine.drug - Abstract
Drugs used for lowering the glucose level in the blood are called hypoglycemic agents. Changes in the level of glucose in the blood can be caused by various reasons, the primary cause being diabetes mellitus. Diabetes mellitus is a metabolic disease associated with a high level of blood sugar and as a rule, disturbance of carbohydrate, lipid, and protein metabolism. Insulin and other hypoglycemic agents are used to treat diabetes mellitus. Insulin, a pancreatic hormone, is a specific antidiabetic agent, especially for type I diabetes. In the body, insulin is synthesized by β-cells of Langerhans islets in the pancreas. The rate of formation changes depending on the type of food consumed, gastrointestinal hormones, and neuronal control. The chapter describes the specific uses on insulin, its mechanish and chemical structure. For patients with type II diabetes, in which endogenic secretion of insulin functions to some degree, a number of very effective hypoglycemic drugs are prescribed. The chapter discusses some of the major synthetic drugs hypoglycemic drugs, such as Tolbutamide, Chlorpropamide, Acetohexamide, Tolazamide, Glyburide, and Glipizide. more...
- Published
- 2006
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49. Nitrosierungen an Hydrazinderivaten, 6. Mitt.: Neuartige Reaktion oraler Antidiabetica vom Sulfonylsemicarbazid-Typ unter nitrosierenden Bedingungen
- Author
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Wolfgang Hanefeld and Michael Hartmann
- Subjects
Sulfonyl ,chemistry.chemical_classification ,Stereochemistry ,Chemistry ,Pharmaceutical Science ,Glisoxepide ,Tolazamide ,chemistry.chemical_compound ,Drug Discovery ,Nitrosation ,medicine ,Glisoxepid ,Hydrazine derivatives ,medicine.drug - Abstract
Orale Antidiabetica vom Sulfonylsemicarbazid-Typ wie Tolazamid (1) und Glisoxepid (2) wurden unter milden nitrosierenden Bedingungen, auch annahernd physiologischen in vitro Bedingungen, nach einem neuartigen Reaktionsverlauf in Sulfonyltriazene 3a, b umgewandelt. Modellverbindungen mit N4-Acyl-semicarbazidstruktur 4 zeigen abweichendes Reaktionsverhalten, wobei Saureamide 5 neben Nitrosaminen 6 gebildet werden. Nitrosations with Hydrazine Derivatives, VI: Novel Reaction of Oral Antidiabetics of the Sulfonylsemicarbazide Type under Nitrosating Conditions Oral antidiabetics of the sulfonylsemicarbazide type like Tolazamide (1) and Glisoxepide (2) were transformed under mild nitrosating conditions, even nearly physiological in vitro conditions, to sulfonyl triazenes 3a, b by a novel reaction pathway. Model compounds with N4-Acyl-semicarbazide structure 4 showed different reaction behaviour yielding carbonamides 5 and nitrosamines 6. more...
- Published
- 1993
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50. Pharmacology of human sulphonylurea receptor SUR1 and inward rectifier K+ channel Kir6.2 combination expressed in HEK-293 cells
- Author
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Gopalakrishnan, Murali, Molinari, Eduardo J, Shieh, Char-Chang, Monteggia, Lisa M, Roch, Jean-Marc, Whiteaker, Kristi L, Scott, Victoria E S, Sullivan, James P, and Brioni, Jorge D
- Subjects
endocrine system ,Potassium Channels ,Receptors, Drug ,Recombinant Fusion Proteins ,Tolbutamide ,Gene Expression ,Deoxyglucose ,Sulfonylurea Receptors ,Tritium ,Binding, Competitive ,Fluorescence ,Cell Line ,Membrane Potentials ,Radioligand Assay ,Cations ,Glyburide ,Humans ,RNA, Messenger ,Potassium Channels, Inwardly Rectifying ,Dose-Response Relationship, Drug ,Diazoxide ,Tolazamide ,Electric Stimulation ,Electrophysiology ,Sulfonylurea Compounds ,Papers ,ATP-Binding Cassette Transporters ,Oligomycins ,Glipizide - Abstract
1. The pharmacological properties of K(ATP) channels generated by stable co-expression of the sulphonylurea receptor SUR1 and the inwardly rectifying K(+) channel Kir6.2 were characterized in HEK-293 cells. 2. [(3)H]-Glyburide (glibenclamide) bound to transfected cells with a B(max) value of 18.5 pmol mg(-1) protein and with a K(D) value of 0.7 nM. Specific binding was displaced by a series of sulphonylurea analogues with rank order potencies consistent with those observed in pancreatic RINm5F insulinoma and in the brain. 3. Functional activity of K(ATP) channels was assessed by whole cell patch clamp, cation efflux and membrane potential measurements. Whole cell currents were detected in transfected cells upon depletion of internal ATP or by exposure to 500 microM diazoxide. The currents showed weak inward rectification and were sensitive to inhibition by glyburide (IC(50)=0.92 nM). 4. Metabolic inhibition by 2-deoxyglucose and oligomycin treatment triggered (86)Rb(+) efflux from transfected cells that was sensitive to inhibition by glyburide (IC(50)=3.6 nM). 5. Diazoxide, but not levcromakalim, evoked concentration-dependen decreases in DiBAC(4)(3) fluorescence responses with an EC(50) value of 14.1 microM which were attenuated by the addition of glyburide. Diazoxide-evoked responses were inhibited by various sulphonylurea analogues with rank order potencies that correlated well with their binding affinities. 6. In summary, results from ligand binding and functional assays demonstrate that the pharmacological properties of SUR1 and Kir6.2 channels co-expressed in HEK-293 cells resemble those typical of native K(ATP) channels described in pancreatic and neuronal tissues. more...
- Published
- 2000
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