33 results on '"Ceftizoxime analogs & derivatives"'
Search Results
2. Study of the structure and dynamics at various parts of the antibacterial drug molecule cefpodoxime proxetil.
- Author
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Dey KK and Ghosh M
- Subjects
- Magnetic Resonance Spectroscopy, Nuclear Magnetic Resonance, Biomolecular methods, Cefpodoxime Proxetil, Anti-Bacterial Agents pharmacology, Ceftizoxime analogs & derivatives
- Abstract
The structure and dynamics of cefpodoxime proxetil are elucidated by measuring chemical shift anisotropy (CSA) tensor, spin-lattice relaxation time, and local correlation time at twenty-one crystallographically different
13 C nuclei sites. The principal components of CSA tensor of cefpodoxime proxetil are extracted by the two-dimensional phase adjusted sinning sideband (2DPASS) cross-polarization magic angle spinning (CP-MAS) solid-state NMR experiment, and the spin-lattice relaxation time is measured by the method outlined by Torchia(T1CP). The local correlation time is calculated by bearing in mind that the spin-lattice relaxation mechanism of13 C nuclei is mainly governed by the CSA interaction and the heteronuclear dipole-dipole interaction. The aminothiazole ring, β-lactam ring, and dihydrothiazine ring provide stability to the drug molecule and increase the affinity of the drug to penicillin-binding proteins (PBPs) receptors. The principal components of CSA parameters, spin-lattice relaxation time, and local correlation time vary substantially for carbon nuclei residing on these three rings. These signify that not only the electronic environment, but the molecular conformation, and the local dynamics are also altered within the ring. The substitution of the acyl side chain, oxime group, and the aminothiazole ring at the C7 position of the β-lactam ring enhances the antibacterial activity and the binding affinity of the drug. A huge variation of the spin-lattice relaxation time and local correlation time is observed in those regions. The change in the electron charge distribution and nuclear spin dynamics at different parts of the drug molecule is clear by CSA and spin-lattice relaxation measurements, which will enrich the field "NMR crystallography"., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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3. Validated HPLC method for the pharmacokinetic study of oral extended-release cefpodoxime proxetil chitosan-alginate beads in rabbits.
- Author
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Mujtaba A and Kohli K
- Subjects
- Administration, Oral, Animals, Ceftizoxime administration & dosage, Ceftizoxime chemistry, Ceftizoxime pharmacokinetics, Drug Carriers chemistry, Glucuronic Acid chemistry, Hexuronic Acids chemistry, Limit of Detection, Linear Models, Rabbits, Cefpodoxime Proxetil, Alginates chemistry, Ceftizoxime analogs & derivatives, Chitosan chemistry, Chromatography, High Pressure Liquid methods, Drug Liberation, Microspheres
- Abstract
The aim of this study is to develop a simple and applicable HPLC method for the detection of cefpodoxime acid (CFA) in rabbit plasma after oral administration of cefpodoxime proxetil (CFP) loaded chitosan-alginate (CH-ALG) beads formulation. CFP is a prodrug that is deesterified in vivo to its active metabolite CFA to exhibit antibiotic activity. Chromatographic separation of CFA and internal standard (IS) was achieved by a RP18(C18), Phenomenax®100, (250×4.6mm) with the mobile phase consisting of (0.02mol/l (20mM) ammonium acetate solution and acetonitrile (92:8, v/v, pH=4.6) at a flow rate of 1.0ml/min. The method was validated according to the requirements of US-FDA guidelines for bioanalytical method validation. The linear regression analysis for the calibration plots showed good linear relationship (R
2 =0.9905) in the working concentration range of 0.5-50μg/ml. The limits of detection and quantification (S/N=3) were 0.069 and 0.136μg/ml. Plasma CFA levels were successfully determined in rabbit with satisfactory precision and accuracy. The analyte was found to be stable after a number of stability studies. The proposed HPLC method was successfully applied to pharmacokinetic study in rabbits for CFP loaded CH-ALG beads and marketed immediate release (IR) tablets. All pharmacokinetic parameters were assessed., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
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4. In vitro/in vivo evaluation of HPMC/alginate based extended-release matrix tablets of cefpodoxime proxetil.
- Author
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Mujtaba A and Kohli K
- Subjects
- Animals, Ceftizoxime chemistry, Ceftizoxime therapeutic use, Delayed-Action Preparations, Drug Liberation, Drug Stability, Glucuronic Acid chemistry, Hexuronic Acids chemistry, Humans, Hydrogen-Ion Concentration, Kinetics, Rabbits, Tablets therapeutic use, Cefpodoxime Proxetil, Alginates chemistry, Ceftizoxime analogs & derivatives, Chemistry, Pharmaceutical, Tablets chemistry
- Abstract
The purpose of this research was to assessment of antimicrobial activity and in vitro/in vivo evaluation of cefpodoxime proxetil extended-release (ER) tablet for once daily administration. The tablets were prepared using combination of biodegradable polysaccharides including hydroxypropyl methylcellulose and sodium alginate as matrix material to achieve pH-independent ER release. The tablets were found within the permissible limits for various physicochemical parameters. The in vitro drug release showed that the drug was released over a period of 24h in a sustained release manner. The drug release followed Higuchi kinetics as these plots showed the highest linearity (R(2)=0.9833), but a close relationship was also observed with zero-order kinetics (R(2)=0.9088) and the drug release mechanism was found to be of anomalous or non-Fickian type. Further, in vitro drug release was assessed by antimicrobial assay and it revealed that drug release through 24h periods was above the MIC. In vivo investigation in rabbits showed ER pharmacokinetic profile of cefpodoxime from the matrix tablets. A good correlation of drug absorption in vivo and drug release in vitro (R(2)=0.9785) was observed. These results suggested that the investigated CFP matrix tablets have a potential for extended-release dosage forms., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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5. Formulation of extended release cefpodoxime proxetil chitosan-alginate beads using quality by design approach.
- Author
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Mujtaba A, Ali M, and Kohli K
- Subjects
- Anti-Infective Agents chemistry, Anti-Infective Agents pharmacology, Calcium Chloride chemistry, Ceftizoxime chemistry, Ceftizoxime pharmacology, Delayed-Action Preparations, Escherichia coli drug effects, Glucuronic Acid chemistry, Hexuronic Acids chemistry, Kinetics, Particle Size, Staphylococcus aureus drug effects, Surface Properties, Cefpodoxime Proxetil, Alginates chemistry, Ceftizoxime analogs & derivatives, Chemistry, Pharmaceutical methods, Chitosan chemistry, Microspheres
- Abstract
The purpose of this work was to develop and characterize chitosan-alginate beads for the extended delivery of cefpodoxime proxetil (CFP), to understand the impact of formulation and process parameters on the critical quality attributes (CQAs) using a quality-by-design approach. For this, a study was performed with various formulation and process parameters to determine their impact on CQAs of beads, which were determined to be time for 80% of the drug released (T80%), particle size, and encapsulation efficiency. The beads of CFP were optimized using a three-factor, three-level Box-Behnken design. A formulation comprising of 4.38% (w/v) alginate, 1.39% (w/v) chitosan and 6.82% (w/v) calcium chloride was found to fulfill requisites of an optimum formulation. In vitro release studies showed that the drug is released from the optimized formulation over a period of 24h in a sustained release manner, primarily by non-Fickian diffusion. The optimized formulation was characterized by DSC, FTIR, XRD and SEM analysis. Antimicrobial studies revealed that the release of the drug over 24h periods was above the minimum concentration required for inhibition of microbial growth. This research highlights the level of understanding that can be accomplished through a well designed study based on the approach of QbD., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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6. Impact of 2011 French guidelines on antibiotic prescription for acute otitis media in infants.
- Author
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Levy C, Pereira M, Guedj R, Abt-Nord C, Gelbert NB, Cohen R, Alberti C, Gajdos V, and Angoulvant F
- Subjects
- Acute Disease, Amoxicillin administration & dosage, Amoxicillin adverse effects, Amoxicillin therapeutic use, Amoxicillin-Potassium Clavulanate Combination therapeutic use, Ceftizoxime analogs & derivatives, Ceftizoxime therapeutic use, Child, Preschool, Drug Resistance, Microbial, Drug Utilization statistics & numerical data, Emergency Service, Hospital statistics & numerical data, France, Guideline Adherence, Humans, Inappropriate Prescribing prevention & control, Inappropriate Prescribing statistics & numerical data, Infant, Multicenter Studies as Topic statistics & numerical data, Pediatrics statistics & numerical data, Practice Patterns, Physicians' statistics & numerical data, Practice Patterns, Physicians' trends, Private Practice statistics & numerical data, Cefpodoxime Proxetil, Anti-Bacterial Agents therapeutic use, Otitis Media drug therapy, Practice Guidelines as Topic
- Abstract
Objective: In 2011, new guidelines on antibiotic prescription for acute otitis media (AOM) were published in France to decrease the use of third generation cephalosporins that promote the carriage of extended-spectrum beta-lactamase producing Escherichia coli. Our objective was to assess the impact of the 2011 French recommendations on the type of antibiotics prescribed for AOM., Methods: Fourteen thousand six hundred and sixty-one children, 6 to 24 months of age, presenting with AOM were included in 2 studies, between November 1, 2009 and October 31, 2012. The first one was conducted with the support of 62 private practice pediatricians; the second one was conducted in 7 pediatric emergency departments. Three periods of 1 year each were defined., Results: Antibiotics were prescribed in 12,471 (85.1%) of cases of AOM during the study period. Amoxicillin prescriptions was multiplied by 25, between the first year (2.6%) and the last year (66.1%). Conversely, prescriptions of cefpodoxime proxetil and amoxicillin-clavulanic acid decreased from 33.6% and 62.0% in the first year to 5.2% and 27.7% in the last year, respectively. This trend was observed in both private practices and in the pediatric emergency departments., Conclusion: Amoxicillin became the most frequently prescribed antibiotic for AOM in 2012, complying with the 2011 French guidelines, while the proportion of prescribed broad-spectrum antibiotics decreased. Our study highlights the importance of guidelines to decrease the prescription of broad-spectrum antibiotics, a crucial factor in the prevention of antibiotic resistance., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)
- Published
- 2014
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7. Highly sensitive and selective high-performance liquid chromatography method for bioequivalence study of cefpodoxime proxetil in rabbit plasma via fluorescence labeling of its active metabolite.
- Author
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Ahmed S, Abdel-Wadood HM, and Mohamed NA
- Subjects
- Animals, Ceftizoxime blood, Ceftizoxime metabolism, Ceftizoxime pharmacokinetics, Chromatography, High Pressure Liquid instrumentation, Fluorescent Dyes chemistry, Oxazoles chemistry, Rabbits, Sensitivity and Specificity, Sulfonamides chemistry, Therapeutic Equivalency, Cefpodoxime Proxetil, Ceftizoxime analogs & derivatives, Chromatography, High Pressure Liquid methods
- Abstract
Cefpodoxime proxetil (CFP), a broad-spectrum third-generation cephalosporin, has been used most widely in the treatment of respiratory and urinary tract infections. For bioequivalence study of CFP in rabbit plasma, it was necessary to develop a highly sensitive and selective high-performance liquid chromatographic (HPLC) method with fluorescence (FL) detection. The pre-column labeling of cefpodoxime acid (CFA) (active metabolite) with an efficient benzofurazan type fluorogenic reagent, 4-N,N-dimethyl aminosulfonyl-7-fluoro-2,1,3-benzoxadiazole (DBD-F) was carried out in the present study in 100mM borate buffer (pH=8.5) at 50°C for 15min. The obtained fluorescent products were separated on C18 column with an isocratic elution of the mobile phase, which consists of 10mM phosphate buffer (pH=3.5)/CH3CN (70:30, v/v). The fluorescent product (DBD-CFA) was detected fluorimetrically at 556nm with an excitation wavelength of 430nm. Cefotaxime sodium was used as internal standard. The method was validated according to the requirements of US-FDA guidelines. The correlation coefficient of 0.999 was obtained in the concentration ranges of 10-1000ngmL(-1). The limits of detection and quantification (S/N=3) were 3 and 10ngmL(-1), respectively. Plasma CFA levels were successfully determined in rabbit with satisfactory precision and accuracy. The proposed HPLC-FL method was successfully applied to study bioequivalence in rabbits for two formulations of different brands contained CFP (prodrug) in a randomized, two-way, single-dose, crossover study and all pharmacokinetic parameters for the two formulations were assessed., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
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8. AuNPs-poly-DAN modified pyrolytic graphite sensor for the determination of Cefpodoxime Proxetil in biological fluids.
- Author
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Yadav SK, Agrawal B, and Goyal RN
- Subjects
- Anti-Bacterial Agents pharmacokinetics, Ceftizoxime analysis, Ceftizoxime pharmacokinetics, Electrochemical Techniques, Graphite chemistry, Humans, Pharmaceutical Preparations chemistry, Urine chemistry, Cefpodoxime Proxetil, Anti-Bacterial Agents analysis, Ceftizoxime analogs & derivatives, Gold chemistry, Metal Nanoparticles chemistry, Naphthalenes chemistry
- Abstract
A sensitive and selective electrochemical method for Cefpodoxime Proxetil (CP) determination has been developed by incorporating gold nanoparticles (AuNPs) onto the poly-1,5-diaminonapthalene layer (p-DAN) coated pyrolytic graphite. The modified sensor was characterized by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The sensor exhibited an effective catalytic response towards oxidation of CP with excellent reproducibility and stability. The peak current of CP was found to be linear in the range of 0.1-12 μM and detection limit and sensitivity of 39 nM (S/N=3) and 4.621 μA μM(-1), respectively, were observed. The method was successfully applied for the determination of CP in pharmaceutical formulations and human urine samples. The common metabolites present in human urine such as uric acid, ascorbic acid, xanthine and hypoxanthine did not interfere in the determination. A comparison of the results obtained by using developed method with high performance liquid chromatography (HPLC) indicated a good agreement. The method is simple, sensitive, rapid and precise and is useful for the routine determination of CP in pharmaceutical dosages and biological samples., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
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9. Simultaneous quantification of cefpodoxime proxetil and clavulanic acid in human plasma by LC-MS using solid phase extraction with application to pharmacokinetic studies.
- Author
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Dubala A, Nagarajan JS, Vimal CS, and George R
- Subjects
- Ceftizoxime blood, Chromatography, Liquid economics, Chromatography, Liquid methods, Humans, Mass Spectrometry economics, Sensitivity and Specificity, Solid Phase Extraction economics, Cefpodoxime Proxetil, Anti-Bacterial Agents blood, Ceftizoxime analogs & derivatives, Clavulanic Acid blood, Mass Spectrometry methods, Solid Phase Extraction methods
- Abstract
A simple, rapid and selective high performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS) method was developed and validated for the simultaneous estimation of cefpodoxime proxetil (CDPX) and clavulanic acid (CA) in human plasma. Extraction of samples was done by solid phase extraction technique (SPE) and chloramphenicol used as internal standard. Chromatographic separation was carried out on a reverse phase Princeton SPHER C18 (150mm×4mm i.d., 5μm) column using mixture of methanol: acetonitrile: 2mM ammonium acetate (25:25:50, v/v, pH 3.5) at 0.8mL/min flow rate. Detection was performed on a single quadrupole MS by selected ion monitoring (SIM) mode via APCI source. The calibration curve was linear within the concentration range, 0.04-4.4μg/mL and 0.1-10.0μg/mL for CDPX and CA respectively. Pharmacokinetic parameters of tablet (CDPX 200mg, CA 125mg) were evaluated. Cmax, Tmax, T1/2, elimination rate constant (Kel), AUC0-t, and AUC0-∞ of tablet were 2.13±0.06μg/mL, 2h, 3.05±0.15h, 0.24±0.37h(-1), 6.81±0.14μg h/mL and 7.72±0.23μg h/mL respectively for cefpodoxime (CP), 5.34±0.28μg/mL, 2h, 2.73±0.25h, 0.26±0.31h(-1), 15.37±0.16μg h/mL and 16.59±0.53μg h/mL respectively for CA., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
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10. Prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae in meat products sold in Navarra, Spain.
- Author
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Ojer-Usoz E, González D, Vitas AI, Leiva J, García-Jalón I, Febles-Casquero A, and Escolano Mde L
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Aztreonam pharmacology, Cattle, Cefotaxime pharmacology, Ceftazidime pharmacology, Ceftizoxime analogs & derivatives, Ceftizoxime pharmacology, Drug Resistance, Multiple, Bacterial drug effects, Enterobacteriaceae growth & development, Microbial Sensitivity Tests, Poultry, Prevalence, Spain, Swine, beta-Lactam Resistance drug effects, beta-Lactamases genetics, Cefpodoxime, Enterobacteriaceae isolation & purification, Food Contamination analysis, Food Microbiology, Meat Products microbiology, beta-Lactamases metabolism
- Abstract
Patterns of resistance in β-lactamase-producing Enterobacteriaceae family were investigated in isolates from 141 meat products (beef, poultry and pork) purchased in Spain. The strains that grow in ChromID ESBL agar plates were confirmed using the paired disk diffusion method. Resistance to amoxicillin/clavulanic acid, ceftazidime, ceftriaxone, aztreonam, cefpodoxime, gentamicin, doxycycline, cotrimoxazol, norfloxacin, piperacillin/tazobactam, fosfomycin and cefoxitin were tested following CLSI recommendations. Minimum inhibitory concentrations were determined by the MicroScan® NM37 panel and β-lactamase genes were detected using multiplex PCR and sequencing. Results show poultry as the meat product having the highest prevalence (84%), with Escherichia coli being the predominant bacteria (71.3%). Predominant β-lactamase types were CTX-M (37.8%), followed by CTX-M+TEM combination (20.7%), TEM (17%), SHV (12.2%), TEM+SHV combination (10.9%) and OXA (1.2%). 93.9% of the strains were resistant to one or more β-lactam antibiotics. Results indicate a widespread distribution of ESBL-producing Enterobacteriaceae in meat products, with a high rate of β-lactam resistance and a low rate of AmpC cephalosporinase-producing strains., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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11. An efficient one-pot reaction for selective fluorimetric determination of cefpodoxime and its prodrug.
- Author
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Mohamed NA, Abdel-Wadood HM, and Ahmed S
- Subjects
- Ceftizoxime analysis, Ceftizoxime urine, Chemistry, Pharmaceutical, Humans, Naphthoquinones chemistry, Reproducibility of Results, Cefpodoxime, Cefpodoxime Proxetil, Ceftizoxime analogs & derivatives, Fluorometry methods, Prodrugs analysis
- Abstract
Cefpodoxime proxetil (CFP), an oral third-generation cephalosporin, is a prodrug that is de-esterified in vivo to its active metabolite, cefpodoxime acid (CFA). Therefore, this study aimed to develop a facile and efficient one-pot reaction for selective and sensitive determination of CFA and its prodrug (CFP). The method was based on single-step reaction between CFP or CFA and 1,2-naphthoquinone-4-sulfonate (NQS) as a selective derivatizing reagent in alkaline medium without heating, extraction or reduction steps as usual for NQS derivatization reactions. The fluorescence of the formed NQS-derivative was monitored directly at emission wavelength of 440 nm after excitation at 330 nm. The method can easily be implemented in plating facilities by operators and/or incorporated in on-line derivatization reaction. The correlation coefficients of 0.9991 and 0.9984 were obtained in the concentration ranges of 50-2000 ng mL(-1) for CFA and CFP, respectively. The detection limits were 9.17 and 9.48 ng mL(-1) for CFA and CFP, respectively. The method was validated in accordance with the requirements of ICH guidelines and shown to be suitable for their efficient and sensitive determinations. The developed method was successfully applied for selective determination of CFP in pure form and in pharmaceutical dosage forms as well as CFA in human urine after single dose of CFP without prior need for separation. The method is valuable for quality control laboratories for monitoring of CFP and its active metabolite CFA., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2011
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12. Ionic liquids as superior solvents for headspace gas chromatography of residual solvents with very low vapor pressure, relevant for pharmaceutical final dosage forms.
- Author
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Laus G, Andre M, Bentivoglio G, and Schottenberger H
- Subjects
- Ceftizoxime analogs & derivatives, Ceftizoxime chemistry, Imidazoles chemistry, Organophosphorus Compounds chemistry, Pharmaceutical Preparations chemistry, Reproducibility of Results, Sensitivity and Specificity, Thiophenes chemistry, Vapor Pressure, Cefpodoxime Proxetil, Excipients analysis, Gas Chromatography-Mass Spectrometry methods, Ionic Liquids chemistry, Solvents analysis
- Abstract
1-n-Butyl-3-methylimidazolium dimethyl phosphate (BMIM DMP) was identified as the most suitable ionic liquid as solvent for the headspace gas chromatographic analysis of solvents with very low vapor pressure such as dimethylsulfoxide, N-methylpyrrolidone, sulfolane, tetralin, and ethylene glycol in a realistic matrix of commonly used excipients (carboxymethylcellulose, magnesium stearate, guar flour, and corn starch) in pharmaceutical products. Limits of quantification and limits of detection were in the low microgram per gram range. The detection of traces of sulfolane in a real sample of tablets containing the drug cefpodoxim proxetil demonstrated the applicability of the method.
- Published
- 2009
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13. Application of high-performance liquid chromatography hyphenated techniques for identification of degradation products of cefpodoxime proxetil.
- Author
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Fukutsu N, Kawasaki T, Saito K, and Nakazawa H
- Subjects
- Ceftizoxime analysis, Ceftizoxime chemistry, Drug Stability, Hydrogen-Ion Concentration, Magnetic Resonance Spectroscopy methods, Molecular Structure, Reproducibility of Results, Spectrometry, Mass, Electrospray Ionization methods, Spectrophotometry, Infrared methods, Temperature, Cefpodoxime Proxetil, Ceftizoxime analogs & derivatives, Chromatography, High Pressure Liquid methods
- Abstract
Application of the HPLC hyphenated techniques of LC-MS, LC-NMR and solvent-elimination LC-IR was demonstrated by the identification of the degradation products of a third generation cephalosporin antibiotic, cefpodoxime proxetil, in solid state, drug formulation and solution. Molecular weight and fragment information were obtained by LC-MS, and detailed structural information was confirmed by LC-NMR. Information on the carboxyl functional group obtained by solvent-elimination LC-IR was useful for confirmation of the ester hydrolysis. The degradation products were successfully identified without complicated isolation or purification processes.
- Published
- 2006
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14. Development and validation of isomer specific RP-HPLC method for quantification of cefpodoxime proxetil.
- Author
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Kakumanu VK, Arora VK, and Bansal AK
- Subjects
- Animals, Ceftizoxime analysis, Ceftizoxime pharmacokinetics, Drug Stability, Intestinal Absorption, Isomerism, Male, Prodrugs analysis, Rats, Rats, Sprague-Dawley, Reproducibility of Results, Sensitivity and Specificity, Cefpodoxime Proxetil, Ceftizoxime analogs & derivatives, Chromatography, High Pressure Liquid methods
- Abstract
The present work explains the development and validation of a simple and reliable isomer specific liquid chromatographic method for the quantitative determination of cefpodoxime proxetil (CP) in rat in situ intestinal perfusate samples. Chromatography was carried out by reversed-phase technique on a C-18 column with a mobile phase composed of 20 mM ammonium acetate buffer (pH 5.0) and acetonitrile in the ratio of 62:38 pumped at a flow-rate of 1 ml/min. The detection was carried out at 235 nm and a column temperature of 30 degrees C. The method was evaluated for the various validation parameters, such as linearity, accuracy, precision, LOD, LOQ, specificity, selectivity, and sample stability. The results of intra- and inter-day validation (n = 3) showed the method to be efficient and the same was applied in an in situ permeability study conducted for CP in rats.
- Published
- 2006
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15. An improved method for preparation of cefpodoxime proxetil.
- Author
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Rodríguez JC, Hernández R, González M, Rodríguez Z, Tolón B, Velez H, Valdés B, López MA, and Fini A
- Subjects
- Acylation, Administration, Oral, Benzothiazoles, Cephalosporins chemistry, Chemistry, Pharmaceutical, Drug Compounding, Cefpodoxime Proxetil, Acetates chemical synthesis, Anti-Bacterial Agents chemical synthesis, Ceftizoxime analogs & derivatives, Ceftizoxime chemical synthesis, Thiazoles chemical synthesis
- Abstract
Cefpodoxime proxetil, a third-generation cephalosporin for oral administration, was synthesized by a method based on the following sequence of reactions: acylation of 7-aminocephalosporanic acid (7-ACA) with S-benzothiazol-2-yl(2-amino-4-thiazolyl)(methoxyimino)thioacetate (MAEM), chloroacetylation of the cefotaxime formed with chloroacetyl chloride, esterification of the acid function with 1-iodoethyl isopropyl carbonate and final cleavage of chloroacetamide protective group by treatment with thiourea in N,N-dimethylacetamide. The developed procedure allows us to obtain better yields of cefpodoxime proxetil and to eliminate the final purification step by column chromatography, necessary during the synthesis of this antibiotic by the previously reported methods.
- Published
- 2003
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16. Intracerebroventricular injection of the antibiotic cefoselis produces convulsion in mice via inhibition of GABA receptors.
- Author
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Yamazaki S, Mochizuki Y, Terai T, Sugimoto M, Uchida I, Matsuoka N, and Mutoh S
- Subjects
- Animals, Anti-Bacterial Agents administration & dosage, Bicuculline antagonists & inhibitors, Bicuculline toxicity, Carbamazepine pharmacology, Ceftizoxime administration & dosage, Dizocilpine Maleate pharmacology, Dose-Response Relationship, Drug, Excitatory Amino Acid Agonists pharmacology, GABA Modulators pharmacology, GABA-A Receptor Agonists, Injections, Intraventricular, Male, Mice, Mice, Inbred ICR, N-Methylaspartate antagonists & inhibitors, N-Methylaspartate pharmacology, Phenobarbital pharmacology, Phenytoin pharmacology, Sodium Channel Blockers pharmacology, Anti-Bacterial Agents toxicity, Anticonvulsants pharmacology, Ceftizoxime analogs & derivatives, Ceftizoxime toxicity, GABA Antagonists, Receptors, GABA drug effects, Seizures chemically induced
- Abstract
A majority of beta-lactam antibiotics (e.g., cephalosporins and penicillins) have convulsive activity to a greater or lesser extent. (6R,7R)-3-[[3-Amino-2-(2-hydroxyethyl)-2H-pyrazol-1-ium-1-yl]methyl]-7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetylamino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate monosulfate (cefoselis), a newly developed injectable beta-lactam antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA), might induce convulsions if cerebral concentrations become highly elevated. In the present study, we examined whether or not cefoselis had convulsive activity after direct brain administration, and we attempted to clarify the pharmacological mechanism of action. When cefoselis was injected into the lateral ventricle of the mouse brain at doses higher than 20 microg/animal, it produced convulsions dose-dependently. Cefoselis (50 microg/animal)-induced convulsions were prevented by pretreatment with 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), diazepam and phenobarbital (ED(50) values (mg/kg) of 0.78, 1.59 and 33.0, respectively), but not by carbamazepine or phenytoin. When the effects of these anticonvulsants on the convulsions induced by intracerebral injection of bicuculline methiodide (BMI) or N-methyl-D-aspartate (NMDA) were investigated, the inhibitory profile of anticonvulsants on cefoselis-induced convulsions was similar to those induced by BMI (125 ng/animal) but differed markedly in their inhibitory activity on NMDA (100 ng/animal)-induced convulsions, which were not inhibited by diazepam. These results suggest that cefoselis may be convulsive at higher concentrations through a mechanism involving inhibition of gamma-aminobutyric acid (GABA)(A) receptors.
- Published
- 2002
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17. Cefcapene inactivates chromosome-encoded class C beta-lactamases.
- Author
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Alba J, Ishii Y, Galleni M, Frère JM, Ito M, and Yamaguchi K
- Subjects
- Ceftizoxime pharmacology, Chromosomes, Bacterial, Drug Stability, Kinetics, beta-Lactamases genetics, Cefpodoxime, Ceftizoxime analogs & derivatives, Cephalosporins pharmacology, Enzyme Inhibitors pharmacology, beta-Lactamase Inhibitors
- Abstract
The stability of cefcapene and cefpodoxime, oral antibacterial cephalosporins, toward different classes of beta-lactamases was evaluated. For the class A beta-lactamases, TEM-1, SHV-1, and NMC-A, only the steady-state kinetic parameter ( k(cat)/ Km) values were calculated (3100 - 1.1 x 10(7) M(-1) x s(-1)), because these enzymes have very high Km values for cefpodoxime and cefotaxime. As for class B beta-lactamases L1, IMP-1, and CcrA, in general, similar k(cat)/ Km values were obtained. However, regarding class C beta-lactamases from Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, and Citrobacter freundii, we found major differences in stability between the two compounds. Cefpodoxime acted as a good substrate for the class C beta-lactamases, except for the enzyme from E. cloacae; its k(cat) and Km values were successfully calculated ( k(cat)/ Km, 1.8 x 10(5) - 1.2 x 10(7) M(-1) x s(-1)). On the other hand, cefcapene acted as a poor substrate or an inactivator for class C beta-lactamases; its k(2)/ K value was successfully calculated (8.7 x 10(5) - 7.0 x 10(6) M(-1) x s(-1)). In addition, k(3) values were determined for beta-lactamases from P. aeruginosa (2.3 x 10(-2) x s(-1)) and C. freundii (2.1 x 10(-1) x s(-1)). Even though these values could be calculated, transient inactivation as an enzyme reactivation reaction for all these enzymes was observed. These findings suggest the potential of cephem compounds as inhibitors of class C beta-lactamases.
- Published
- 2002
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18. Electrochemical study of cefetamet-Na and its polarographic determination.
- Author
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Kapetanovic V, Aleksic M, Erceg M, and Veselinovic D
- Subjects
- Ceftizoxime chemistry, Hydrogen-Ion Concentration, Polarography, Ceftizoxime analogs & derivatives
- Abstract
Polarographic behavior of cephalosporin cefetamet-Na (Cef-Na) in aqueous solutions of pH ranging from 1.7 to 12.5 was investigated by applying direct current (dc) polarography, differential pulse polarography (dpp), alternating current (ac) polarography, cyclic voltammetry and electrolysis at constant potential. The characteristics of the corresponding electrode reaction are presented and discussed. The electrode reaction was found to be affected by strong adsorption, strongly and slightly pronounced in acidic and alkaline media, respectively. The methoxyimino group electroreduction was carried out and the mechanistic scheme was suggested. In addition, a sensitive dpp method was proposed for analytical determination of a very low concentrations of Cef-Na.
- Published
- 2000
- Full Text
- View/download PDF
19. [Development of resistance to beta-lactams and other antibiotics of pneumococci isolated from acute otitis media in France: statement of the National Reference Center 1995-1996].
- Author
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Geslin P, Fremaux A, Sissia G, Spicq C, and Georges S
- Subjects
- Acute Disease, Amoxicillin pharmacology, Ceftizoxime analogs & derivatives, Ceftizoxime pharmacology, Cefuroxime pharmacology, Erythromycin pharmacology, Erythromycin therapeutic use, France, Humans, Otitis Media drug therapy, Penicillin Resistance, Penicillins pharmacology, Pneumococcal Infections drug therapy, Serotyping, Streptococcus pneumoniae classification, Streptococcus pneumoniae isolation & purification, Tetracycline pharmacology, Tetracycline therapeutic use, Trimethoprim, Sulfamethoxazole Drug Combination pharmacology, Trimethoprim, Sulfamethoxazole Drug Combination therapeutic use, beta-Lactams pharmacology, Cefpodoxime, Microbial Sensitivity Tests, Otitis Media microbiology, Pneumococcal Infections microbiology, Streptococcus pneumoniae drug effects, beta-Lactam Resistance
- Abstract
Population and Methods: During 1995 and 1996, 393 and 566 strains of Streptococcus pneumoniae, isolated from acute otitis media, were respectively sent to the National Reference Center for Pneumococci by its corresponding centers., Results: The resistance rates for 1995 and 1996 were respectively: for penicillin: 65.4 and 70.3% (18.6 and 24.9% of intermediately resistant strains, 46.8 and 45.4% of fully resistant strains), for erythromycin: 57.5 and 68.5%, for tetracycline: 43.2 and 42.6%, for trimethoprim-sulfamethoxazole: 47.5 and 50.9%. Minimal inhibitory concentrations (MICs) of various betalactams were determined against a representative sample of strains (n = 99)., Conclusion: Amoxicillin, cefpodoxime and cefuroxime MICs remained low against numerous penicillin resistant strains, indicating that these three oral antibiotics (in combination with clavulanate for amoxicillin) have a useful potential for the treatment of acute otitis media when risk factors for pneumococcal penicillin-resistant infections are detected.
- Published
- 1998
- Full Text
- View/download PDF
20. [Maternal and neonatal Pasteurella multocida infection].
- Author
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Escande F, Borde M, and Pateyron F
- Subjects
- Adult, Amoxicillin therapeutic use, Animals, Bites and Stings microbiology, Cefotaxime therapeutic use, Ceftizoxime analogs & derivatives, Ceftizoxime therapeutic use, Cephalosporins therapeutic use, Dogs, Drug Therapy, Combination therapeutic use, Female, Gentamicins therapeutic use, Humans, Infant, Newborn, Male, Netilmicin therapeutic use, Pasteurella Infections drug therapy, Penicillins therapeutic use, Pregnancy, Pregnancy Complications, Infectious drug therapy, Zoonoses, Cefpodoxime, Pasteurella Infections transmission, Pasteurella multocida, Pregnancy Complications, Infectious microbiology
- Abstract
Background: Materno-fetal infection due to Pasteurella multocida is rare; it may be severe in the neonate., Case Report: A 27-year old woman was admitted at 37 weeks' gestation with a history of abdominal cramps. Twenty-four hours after delivery, the mother was febrile (40 degrees C) and was given intravenous cefotaxime (2 days), followed by cefpodoxime (15 days). The newborn was febrile and hypotonic 24 hours after birth; he received an infusion of hydroxyethylamidon and was given cefotaxime (3 days), netilmicin (6 days) and amoxicillin (10 days). Pasteurella multocida was isolated from placenta, blood and gastric fluid in the baby and in blood cultures and vaginal swab in the mother. It was established that the mother was bitten by her dog during the pregnancy and wounded a few days before delivery., Conclusion: This neonate was infected during the delivery and the source of mother's contamination was easy to determinate: pet animals were kept by the family and there was an history of wounds during her pregnancy.
- Published
- 1997
- Full Text
- View/download PDF
21. Antimicrobial prophylaxis in pregnancy: a randomized, placebo-controlled trial with cefetamet-pivoxil in pregnant women with a poor obstetric history.
- Author
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Gichangi PB, Ndinya-Achola JO, Ombete J, Nagelkerke NJ, and Temmerman M
- Subjects
- Acquired Immunodeficiency Syndrome epidemiology, Administration, Oral, Adult, Birth Weight physiology, Ceftizoxime administration & dosage, Ceftizoxime therapeutic use, Cervix Uteri microbiology, Cost-Benefit Analysis, Dose-Response Relationship, Drug, Endometritis economics, Endometritis epidemiology, Endometritis prevention & control, Female, Fetal Death economics, Fetal Death epidemiology, Fetal Death prevention & control, Gonorrhea economics, Gonorrhea epidemiology, Gonorrhea prevention & control, Humans, Infant, Newborn, Kenya epidemiology, Neisseria gonorrhoeae isolation & purification, Pregnancy, Pregnancy Complications, Infectious economics, Pregnancy Complications, Infectious epidemiology, Pregnancy Trimester, Third, Prevalence, Treponemal Infections economics, Treponemal Infections epidemiology, Treponemal Infections prevention & control, Ceftizoxime analogs & derivatives, Pregnancy Complications, Infectious prevention & control, Pregnancy Outcome
- Abstract
Objective: This study was undertaken to measure the impact of a single oral dose of cefetamet-pivoxil on pregnancy outcome in a population with substantial rates of low birth weight and high prevalence rates of maternal infections., Study Design: A total of 320 pregnant women with a poor obstetric history, defined as a history of low birth weight or stillbirth, were randomized to receive a single oral dose of 2 gm of cefetamet-pivoxil or a placebo at a gestational age between 28 and 32 weeks. Patients were assessed at delivery and 1 week post partum for pregnancy outcome, postpartum endometritis, human immunodeficiency virus-1 and gonococcal infections., Results: A total of 253 (79%) women gave birth at the maternity hospital, of whom 210 (83%) attended the follow-up clinic. Overall, 18.1% of these pregnant women were human immunodeficiency virus-1 seropositive, whereas 9.5% had antibodies against Treponema pallidum. There was a significant difference between cefetamet-pivoxil- and placebo-treated women in infant birth weight (2927 gm vs 2772 gm, p = 0.03) and low birth weight (< 2500 gm) rates (18.7% vs 32.8%, p = 0.01, odds ratio 2.1, 95% confidence interval 1.2 to 3.8). The stillbirth rate was 2.2% in the cefetamet-pivoxil group and 4.2% in the placebo group (not significant). Postpartum endometritis was found in 17.3% in the intervention arm versus 31.6% in the placebo group (p = 0.03, odds ratio 2.2, 95% confidence interval 1.1 to 7.6). Neisseria gonorrhoeae was isolated from the cervix in 5 of 103 (4.9%) women in the intervention and in 14 of 101 (13.9%) in the placebo group (p = 0.04, odds ratio 3.2, 95% confidence interval 1.1 to 10.5)., Conclusion: A single oral dose of cefetamet-pivoxil administered to pregnant women with a poor obstetric history seemed to improve pregnancy outcome in this population with high rates of maternal infections. Larger studies should be carried out to examine the public health impact, the feasibility, and the overall cost/benefit ratio of this intervention.
- Published
- 1997
- Full Text
- View/download PDF
22. [Comparative trial of the clinical efficacy and tolerance of cefatrizine (Cefaperos) and cefpodoxime proxetil (Orelox) in superinfections of chronic obstructive bronchopneumopathies in adults in urban practice].
- Author
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Brambilla C, Benhamou D, Guérin JC, Kelkel E, Muir JF, Prud'homme A, Taytard A, and Fauche A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cefatrizine administration & dosage, Cefatrizine adverse effects, Ceftizoxime administration & dosage, Ceftizoxime adverse effects, Ceftizoxime therapeutic use, Female, Humans, Male, Middle Aged, Prodrugs administration & dosage, Prodrugs adverse effects, Urban Health Services, Cefpodoxime Proxetil, Cefatrizine therapeutic use, Ceftizoxime analogs & derivatives, Lung Diseases, Obstructive drug therapy, Prodrugs therapeutic use
- Abstract
In order to compare the clinical efficacy and safety of cefatrizine (Cefaperos) and cefpodoxime proxetil (Orelox) in the treatment of secondarily infected chronic obstructive pulmonary disease (COPD) in adults, a multicentre, randomized, open study was conducted by 60 general practitioners in two parallel groups of patient suffering from COPD complicated by an acute episode of superinfection (Anthoniesen stages 2 and 3). After verification of the eligibility criteria, written consent and randomization, the patients received, for 10 days, either cefatrizine at the dose of 1 g/day or cefpodoxime proxetil at the dose of 400 mg/day. A self-assessment form was given to the patient. A telephone visit was planned for D3. The final visit on D11 +/- 1 evaluated clinical efficacy (success or failure) and safety. The study population was composed of 250 patients with a mean age of 59.9 +/- 15.9 years (sex ratio M/F = 1.5). The principal etiology of COPD was chronic bronchitis in 67.5% of patients, longstanding asthma in 24.5% and emphysema in 6.8%. The mean history of the disease was 13.0 +/- 10.8 years. The Anthoniesen score was equal to 2 in 73.6% of patients, 3 in 8.8% of patients and 1 in 17.6% of patients. No significant difference concerning these criteria was observed between the two study groups. The clinical success rate was equivalent in the two groups. The time to regression of clinical signs tended to be shorter, up until the sixth day (mainly between D4 and D6) for patients treated with cefatrizine (p = 0.09; NS). The clinical safety was considered to be good and was comparable in the two study groups. This study concluded on the equivalent clinical efficacy of cefatrizine and cefpodoxime proxetil in the treatment of superinfections of COPD in general practice (97.5% and 99%, respectively), with a satisfactory and comparable safety, but with a much lower cost of treatment for cefatrizine. This conclusion is particularly important in the context of opposable medical references, as, although the treatment of superinfections of COPD by second and third generation cephalosporins is frequently proposed, the prescription of a less expensive cephalosporin appears to be more relevant.
- Published
- 1995
23. High-performance liquid chromatographic method for the determination of cefpodoxime levels in plasma and sinus mucosa.
- Author
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Camus F, Deslandes A, Harcouet L, and Farinotti R
- Subjects
- Ceftizoxime analysis, Ceftizoxime blood, Ceftizoxime pharmacokinetics, Chromatography, High Pressure Liquid, Humans, Mucous Membrane chemistry, Spectrophotometry, Ultraviolet, Cefpodoxime, Ceftizoxime analogs & derivatives, Paranasal Sinuses chemistry
- Abstract
A selective HPLC method is described for the determination of cefpodoxime levels in plasma and sinus mucosa. Sample preparation included solid-phase extraction with a C8 cartridge. Cefpodoxime and cefaclor (internal standard) were eluted with methanol and analyzed on an optimised system consisting of a C18 stationary phase and a ternary mobile phase (0.05 M acetate buffer pH 3.8-methanol-acetonitrile, 87:103, v/v) monitored at 235 nm. Linearity and both between- and within-day reproducibility were assessed for plasma and sinus mucosa samples. Inter-assay coefficients of variation were lower than 13.6% (n = 10) for plasma (0.2 micrograms/ml) and lower than 12.4% (n = 5) for sinus mucosa (0.25 micrograms/g). The quantification limit was 0.05 micrograms/ml for plasma and 0.13 micrograms/g for tissue. The method was used to study the diffusion of cefpodoxime in sinus mucosa.
- Published
- 1994
- Full Text
- View/download PDF
24. Determination of cefpodoxime levels in chinchilla middle ear fluid and plasma by high-performance liquid chromatography.
- Author
-
Lovdahl MJ, Reher KE, Russlie HQ, and Canafax DM
- Subjects
- Animals, Ceftizoxime analysis, Ceftizoxime blood, Chinchilla, Reproducibility of Results, Spectrophotometry, Ultraviolet, Cefpodoxime, Body Fluids metabolism, Ceftizoxime analogs & derivatives, Chromatography, High Pressure Liquid methods, Ear, Middle metabolism, Otitis Media metabolism
- Abstract
A high-performance liquid chromatographic method has been developed to determine cefpodoxime levels in chinchilla plasma and middle ear fluid (MEF) to be used in studying otitis media. Cefpodoxime and the internal standard, cefuroxime, were separated on an ODS column (250 x 2.1 mm I.D., 5 microns Hypersil), using a mobile phase of 25 mM acetate buffer (pH 4.3)/15 mM triethylamine-acetonitrile (92.5:7.5, v/v). Following elution of cefpodoxime and the internal standard, at 3.5 and 5.9 min respectively, the acetonitrile concentration was increased to 1:1 (v/v) in a step function to elute endogenous compounds retained on the column. Sample preparation involved protein precipitation with acetonitrile. This fast, efficient protein precipitation procedure together with UV detection allows a quantitation limit of 50 ng/ml with a 50-microliters sample size. Recoveries (mean +/- S.D., n = 3) at 0.1 microgram/ml in MEF were 90.3 +/- 2.9% and 88.6 +/- 1.2% for cefpodoxime and cefuroxime respectively. Recoveries (mean +/- S.D., n = 3) at 0.1 microgram/ml in plasma were 72.1 +/- 7.3% and 81.1 +/- 1.1% for cefpodoxime and cefuroxime respectively. The method was evaluated with biological samples taken from chinchillas with middle ear infections after administering cefpodoxime proxetil.
- Published
- 1994
- Full Text
- View/download PDF
25. A comparison of cefpodoxime proxetil and cefaclor in the treatment of acute exacerbation of COPD in adults.
- Author
-
Phillips H, Van Hook CJ, Butler T, and Todd WM
- Subjects
- Acute Disease, Adult, Aged, Bacteria drug effects, Bacteria isolation & purification, Cefaclor adverse effects, Cefaclor pharmacology, Ceftizoxime adverse effects, Ceftizoxime pharmacology, Ceftizoxime therapeutic use, Drug Tolerance, Female, Humans, Lung Diseases, Obstructive microbiology, Male, Microbial Sensitivity Tests, Middle Aged, Prodrugs adverse effects, Prodrugs pharmacology, United States, Cefpodoxime, Cefpodoxime Proxetil, Cefaclor therapeutic use, Ceftizoxime analogs & derivatives, Lung Diseases, Obstructive drug therapy, Prodrugs therapeutic use
- Abstract
In this multicenter, observer-blinded study, 301 patients with signs and symptoms of acute bacterial exacerbation of COPD were randomized (2:1) to receive either cefpodoxime proxetil (200 mg, bid) or cefaclor (250 mg, tid) for 10 days. Clinical and microbiologic evaluations were performed before treatment, during therapy (study days 3 to 5), at the end of therapy (3 to 7 days posttreatment), and at long-term follow-up (4 weeks posttreatment). The most common pretreatment isolates were Haemophilus influenzae, Haemophilus parainfluenzae, and Streptococcus pneumoniae. Significantly (p < 0.001) more bacterial isolates were susceptible in vitro to cefpodoxime (233 of 256, 91 percent) than to cefaclor (215 of 255, 84 percent). There were no statistically significant differences between the two drug regimens in eradication of the initial pathogen (cefpodoxime, 116 of 128, 91 percent; cefaclor, 59 of 64, 92 percent) or end-of-therapy clinical response (cure + proved; cefpodoxime, 99 of 100, 99 percent; cefaclor, 45 of 49, 92 percent) rates for evaluable patients. Both drug treatments were well-tolerated, with a similar incidence of drug-related adverse events (cefpodoxime 11 percent, cefaclor 12 percent). Cefpodoxime (bid) was as safe and effective as cefaclor (tid) in the treatment of acute exacerbation of COPD. The less frequent dosing regimen of cefpodoxime may improve patient compliance compared to those antibiotics that require three or four daily doses.
- Published
- 1993
- Full Text
- View/download PDF
26. Serum and urinary cefpodoxime levels and time killing curves performed in the urine of children presenting urinary tract infections.
- Author
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Casellas JM, Tome G, Exeni R, Grimoldi I, Goldberg M, and Farinati AE
- Subjects
- Anti-Bacterial Agents pharmacology, Anti-Infective Agents, Urinary therapeutic use, Ceftizoxime blood, Ceftizoxime pharmacology, Ceftizoxime therapeutic use, Ceftizoxime urine, Child, Dose-Response Relationship, Drug, Escherichia coli isolation & purification, Escherichia coli Infections microbiology, Female, Humans, In Vitro Techniques, Klebsiella drug effects, Klebsiella isolation & purification, Male, Proteus mirabilis drug effects, Proteus mirabilis isolation & purification, Urinary Tract Infections microbiology, Cefpodoxime, Ceftizoxime analogs & derivatives, Escherichia coli drug effects, Escherichia coli Infections drug therapy, Urinary Tract Infections drug therapy
- Abstract
Since resistance to several oral antimicrobials useful for the treatment of pediatric urinary tract infections (UTI) is overwhelming in Argentina, an in vitro investigation was performed testing 400 isolates obtained from urines of children suffering UTI's, 200 collected in 1990 and 200 in 1991. Their susceptibility against oral antimicrobials marketed in Argentina and appropriate for the treatment of UTI was determined by the agar dilution methods. An increase of the resistance to aminopenicillin combined with beta-lactamase inhibitors and to fluoroquinolones was observed comparing the two periods. Cefpodoxime (CPD), cefixime and fluoroquinolones except norfloxacin were the sole oral antimicrobials showing in vitro activity at the 90 per cent level. Unfortunately fluoroquinolones are not yet approved for pediatric use. Consequently we realized an in vitro and in vivo pharmacokinetic study in order to determine CPD activity against E. coli isolated in UTI cases. Five children (6-10 y) showing E. coli UTI infections received 10 mg/kg/d CPD in a single oral daily dose and were treated up to 10 days, 3 had lower UTI and 2 upper UTI. All patients were clinical and bacteriologically cured. Cultures obtained up to 4 weeks after treatment were negative. CPD serum levels at 2 hours after the first dose of treatment showed a median of 2.7 mg/l (2.3-3.4 range). Bactericidal serum titers at the same time against the patients own strain and an E. coli TEM-1 hyperproducer strain (MIC 4,096 mg/l for ampicillin and 0.5 mg/l for CPD) showed a median value of 1/8 against patients strains and 1/2 against the THP strain.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
27. [Study of the bactericidal effect of cefpodoxime using an in vitro pharmacokinetic model].
- Author
-
Caisson A and Chantot JF
- Subjects
- Ceftizoxime pharmacology, Dose-Response Relationship, Drug, In Vitro Techniques, Prodrugs pharmacology, Cefpodoxime Proxetil, Ceftizoxime analogs & derivatives, Escherichia coli drug effects, Microbial Sensitivity Tests methods, Staphylococcus aureus drug effects, Streptococcus pneumoniae drug effects
- Abstract
Cefpodoxime is a new oral prodrug antibiotic. Following absorption from the proximal intestine, non-specific esterases hydrolyze this cleavable ester, releasing cefpodoxime, a new broad-spectrum third-generation cephalosporin with sustained plasma levels in humans. Cefpodoxime killing kinetics were studied using an in vitro model which simulates the pharmacokinetic profile obtained in healthy volunteers given a single oral dose of cefpodoxime proxetil providing 100, 200 or 400 mg active cefpodoxime. Cefpodoxime exhibited strong antibacterial activity against tested strains of Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus. These results suggest that use of two daily doses of 100 or 200 mg each are appropriate for the treatment of E. coli and S. pneumoniae infections in view of the pharmacokinetic properties of cefpodoxime. Less intensive therapy is probably adequate in uncomplicated community-acquired urinary tract infections. The bactericidal effect of cefpodoxime against S. aureus is prolonged due to a postantibiotic effect.
- Published
- 1991
28. Determination of the third generation oral cephalosporin cefpodoxime in biological fluids by high-speed high-performance liquid chromatography.
- Author
-
Molina F, Jehl F, Gallion C, Penner F, and Monteil H
- Subjects
- Ceftizoxime blood, Ceftizoxime metabolism, Ceftizoxime pharmacokinetics, Ceftizoxime urine, Chromatography, High Pressure Liquid methods, Humans, Indicators and Reagents, Kidney metabolism, Microchemistry, Cefpodoxime, Ceftizoxime analogs & derivatives
- Published
- 1991
29. [RU 51807 (cefpodoxime proxetil). In vitro and in vivo antibacterial activity of a new orally administered active cephalosporin].
- Author
-
Chantot JF and Mauvais P
- Subjects
- Animals, Ceftizoxime chemistry, Ceftizoxime pharmacology, Ceftizoxime therapeutic use, Dose-Response Relationship, Drug, Klebsiella Infections drug therapy, Mice, Streptococcal Infections drug therapy, beta-Lactamases analysis, Cefpodoxime Proxetil, Ceftizoxime analogs & derivatives, Enterobacteriaceae drug effects, Haemophilus influenzae drug effects, Pseudomonas aeruginosa drug effects, Staphylococcus drug effects
- Abstract
Cefpodoxime proxetil (RU 51807) is an enterally absorbed ester prodrug which is rapidly cleaved in vivo after oral administration, with release of the active free acid metabolite cefpodoxime. The in vitro antibacterial activity of the sodium salt of cefpodoxime (RU 51746) against approximately 800 clinical isolates was evaluated comparatively with other orally active beta-lactams. RU 51746 was found to be active against enterobacteria normally susceptible to third generation cephalosporins, with MIC50 values ranging from 0.02 mg/l (Providencia sp) to 5 mg/l (C. freundii). RU 51746 was also active against H. influenzae, including beta-lactamase producing strains (MIC50 0.04 mg/l), oxa-S S. aureus (2,5), beta-hemolytic streptococci (0.05) and S. pneumoniae (0.002). Oxa-R staphylococci and P. aeruginosa were resistant to RU 51746 (MIC50 greater than 40 mg/l for both organisms). The antibacterial activity of RU 51746 was bactericidal in nature and independent from test conditions. The molecule was stable to all the beta-lactamases studied, with the exception of cefuroximase (type Ic). RU 51746 exhibited no strong inhibitory effects on these enzymes, except with Enterobacter P99 (type Ia). A good correlation was found between in vivo activity of RU 51807 and in vitro activity of RU 51746. Cefpodoxime proxetil was found to be more effective than cefaclor in mice with experimental septicemia caused by various streptococci, with a DP50 ratio in the 10-100 range. This advantage was again evidenced for septicemias due to various enterobacteria. In contrast, cefaclor proved more effective in experimental staphylococcus infections. In mice with experimental pneumonia, cefpodoxime proxetil caused sharp falls in K. pneumoniae lung counts. Six days after induction of the infection, 60% of animals under cefpodoxime proxetil had sterile lungs, versus 25% of animals under amoxicillin.
- Published
- 1991
30. [Comparative antibacterial activity of cefpodoxime, cefuroxime and cefaclor against strict anaerobic bacteria].
- Author
-
Dubreuil L, Derriennic M, and Sedallian A
- Subjects
- Anti-Bacterial Agents pharmacology, Ceftizoxime pharmacology, Dose-Response Relationship, Drug, In Vitro Techniques, Cefpodoxime, Bacteria, Anaerobic drug effects, Cefaclor pharmacology, Ceftizoxime analogs & derivatives, Cefuroxime pharmacology, Cephalexin analogs & derivatives, Cephalosporins pharmacology
- Abstract
The in vitro activity of a new cephalosporin (CPX) was assessed against 260 strains of anaerobic bacteria. A comparison was done with two other oral cephalosporins cefaclor (CFA) and cefuroxime (CXM). MICs were determined by an agar-dilution method on wilkins chalgren agar. The three antibiotics had little activity against Bacteroïdes fragilis group. Cefpodoxime was more active than the two other cephalosporins against Fusobacterium and Bacteroïdes spp. At 4 mg/l concentration the percentages of susceptibility were respectively CFA 8% CXM 11% for all the Gram negative bacilli. Inversely, a better activity was detected against Gram positive anaerobes; the three cephalosporins inhibiting respectively CFA 65% CXM 75% CFX 46% of 94 tested strains. All Veillonella spp. and Propionibacteria were inhibited by cefpodoxime 4 mg/l. The activity of the three cephalosporins were similar weak against Gram negative anaerobes but greater against Gram positive strict anaerobes.
- Published
- 1990
31. [In vitro antibacterial activity of RU 51746 (sodium salt of cefpodoxime). Results of a multicenter study].
- Author
-
Soussy CJ, Le Van Thoi J, Kitzis MD, Chanal C, Mounier M, Derlot E, and Vergnaud M
- Subjects
- Ceftizoxime pharmacology, Dose-Response Relationship, Drug, Drug Resistance, Microbial, In Vitro Techniques, Listeria drug effects, Multicenter Studies as Topic, Neisseriaceae drug effects, Pseudomonas drug effects, Staphylococcus drug effects, Cefpodoxime, Anti-Bacterial Agents pharmacology, Ceftizoxime analogs & derivatives, Enterobacteriaceae drug effects, Haemophilus drug effects, Streptococcus drug effects
- Abstract
Cefpodoxime proxetil, a new oral cephalosporin, is the prodrug ester of cefpodoxime. Minimal inhibitory concentrations (MIC) of RU 51746 (sodium salt of cefpodoxime: CPD) were evaluated by agar dilution for 1 696 bacterial strains isolated in 5 hospitals. For Enterobacteriaceae, MIC 50 and 90% were respectively (micrograms/ml): (1) naturally non bêtalactamase producing species: E. coli, Shigella and Salmonella 0.25-0.5; P. mirabilis 0.06-0.12. (II) chromosomal penicillinase producing species: Klebsiella 0.12-1. (III) chromosomal cephalosporinase producing species: E. cloacae and C. freundii 2-greater than 128; S. marcescens 2-64; indole + Proteus 0.25-64; P. stuartii 0.25-16. Activity of CPD was not modified on plasmid mediated penicillinase producing strains, but CPD was inactive on cephalosporinase hyperproducing strains, and on broad spectrum bêtalactamases producing strains. CPD was inactive on P. aeruginosa (MIC greater than or equal to 64) and on A. baumannii (16-pi 128). Haemophilus, regardless on bêtalactamase production status, were very susceptible to CPD (MIC less than or equal to 0.25) and B. catarrhalis was generally inhibited by 0.12 to 1. CPD was poorly active on methicillin susceptible Staphylococci (MIC 50 and 90%: 2-4) and inactive on methicillin resistant strains. Enterococci and Listeria monocytogenes were generally resistant; Streptococci A, B, C, G and Pneumococci were inhibited by low concentration: 0.002 to 0.25 (MIC 50 and 90%: 0.016-0.032) whereas MIC for other Streptococci were 0.004 to 32 (MIC 50 and 90%: 0.25-4). These antibacterial properties placed CPD in excellent position among oral cephalosporins.
- Published
- 1990
32. [Comparative study of the antibacterial activity of cefpodoxime against enterobacteria producing beta lactamases].
- Author
-
Siebor E, Cordin X, Delpech N, Duez JM, and Kazmierczak A
- Subjects
- Anti-Bacterial Agents pharmacology, Ceftizoxime pharmacology, Cephalosporins pharmacology, Dose-Response Relationship, Drug, Drug Resistance, Microbial, Enterobacteriaceae enzymology, Hydrolysis, In Vitro Techniques, Phenotype, Cefpodoxime, Ceftizoxime analogs & derivatives, Enterobacteriaceae drug effects, beta-Lactamases metabolism
- Abstract
Cefpodoxime proxetil (RU 51 807) is the oral prodrug of cefpodoxime (RU 51 763), a third generation cephalosporin. The antibacterial activity of cefpodoxime was compared with the activities of amoxicillin in combination with clavulanic acid (AUG), cefaclor (CCl), cefuroxime (CXM) and cefotaxime (CTX), against species of Enterobacteriaceae showing a resistance pattern against ampicillin (AMP), ticarcillin (TIC), cefalothin (CFT) and cefotaxime (CTX) respectively. For strains AMP and TIC R, CFT and CTX S, MICs 90% of cefpodoxime were 1 mg/l (E. coli), 0.5 (K. pneumoniae), 0.06 (P. mirabilis), 0.5 (Shigella sp.) and 1 (Salmonella sp.); they were 4 to 16 times as high for AUG -CCL -CXM and 4 to 16 times as low for CTX. For K. pneumoniae AMP and TIC R, CFT I/R and CTX S, similar résults were obsereved for the 5 beta-lactam antibiotics, but with an activity 10 times as low. Among the species AMP R, TIC S, CFT R and CTX S, cefpodoxime was active against P. rettgeri, P. stuartii, C. diversus, E. aerogenes and Y. enterocolitica (MICs 90% ranging from 2 to 4 mg/l; from 0.12 to 1 mg/l for CTX) and less active or inactive against P. vulgaris, E. cloacae, S. marcescens, M. morganii and E. coli (MICs 90% ranged from 16 to 32 mg/l; from 1 to 4 mg/l for CTX).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1990
33. Determination of cefetamet and its orally active ester, cefetamet pivoxyl, in biological fluids by high-performance liquid chromatography.
- Author
-
Wyss R and Bucheli F
- Subjects
- Ceftizoxime analysis, Ceftizoxime blood, Ceftizoxime urine, Chromatography, High Pressure Liquid, Humans, Solvents, Spectrophotometry, Ultraviolet, Temperature, Ceftizoxime analogs & derivatives
- Abstract
Two different, simple and rapid high-performance liquid chromatographic methods with ultraviolet detection, using a common sample work-up procedure, were developed for the determination of cefetamet, an in vitro active cephalosporin, and its orally absorbed pivaloyloxymethyl ester, cefetamet pivoxyl. After protein precipitation with perchloric acid, plasma samples were analysed on C18 reversed-phase columns with 4 mM perchloric acid-acetonitrile (83:17, v/v) and 0.1 M phosphate buffer (pH 6.5)-acetonitrile (60:40, v/v) as mobile phases for the determination of cefetamet and cefetamet pivoxyl, respectively. Urine samples were diluted with water and analysed in the same manner, using 4 mM perchloric acid-acetonitrile (85:15, v/v). The limits of quantification were 0.2, 0.5 and 20 micrograms/ml for the determination of cefetamet and cefetamet pivoxyl in plasma and cefetamet in urine, respectively. The intra-assay precision was less than or equal to 1.5% for cefetamet and less than or equal to 2.3% for cefetamet pivoxyl. The inter-assay precision for cefetamet was less than or equal to 2.4%. Cefetamet was stable in human plasma when stored at -20 degrees C for three months or at 22 degrees C for 24 h. For the determination of cefetamet pivoxyl, which was extremely unstable in plasma (greater than 70% degradation in 1 h), samples were drawn into vacutainers containing citric acid and immediately added to sodium fluoride. The method for cefetamet was successfully applied to several thousand plasma and urine samples from humans, dogs and rats. No unchanged drug could be detected in human or dog plasma after the administration of cefetamet pivoxyl.
- Published
- 1988
- Full Text
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