Search

Ethnopharmacological relevance Vitex megapotamica (Spreng.) Moldenke is a deciduous tree, native of South America. Its leaves are traditionally used to treat cardiovascular diseases. This activity is related to the presence of flavonoids, the major compounds of the crude extract. Aim of the study This study investigated the effects of the oral administration of crude extract and standardized fractions from V. megapotamica leaves on lipid profile and on the formation of atherosclerotic plaque in C57BL/6 LDLr-KO mice treated with high-fat diet (HFD). Materials and methods Male C57BL/6 LDLr-KO mice were fed with HFD (cholesterol, 1.25%) for 30 days. They were treated with hydroethanolic extract (500 or 1000 mg/kg/day) or fractions (125 or 250 mg/kg/day). After 30 days of treatment, it was evaluated the serum lipid profile, atherogenic index, and atherosclerotic plaque. Results All doses of the hydroethanolic extract reduced significantly the levels of total cholesterol, triglycerides, LDL-c and the atherogenic index. The n-butanolic fraction also reduced significantly the levels of total cholesterol, triglycerides, LDL-c and the atherogenic index, at all doses, with exception for the triglycerides, which only the lower dose was effective. The residual fraction reduced significantly the levels of total cholesterol, LDL-c and the atherogenic index, at all doses, with exception for the atherogenic index, which only the higher dose was effective. The atherosclerotic plaque formation was impaired only by the lower dose of the hydroethanolic extract. Conclusions Overall, our data suggest that V. megapotamica has potential for the treatment of dyslipidemias.

Poorly water soluble drugs tend to have low bioavailability, however, this can be improved by several methods. One of the most promising strategies is the employment of solid dispersions to increase water solubility and enhance oral bioavailability of these drugs. Nonetheless, the mechanisms of solid dispersion formation may influence the solid-state characteristics and thus the dissolution profile. In this study, rotary evaporation and spray-drying solvent evaporation techniques were used to produce solid dispersions of the anti-allergenic loratadine, a class II drug in the Biopharmaceutical Classification System, with the hydrophilic carrier polyvinylpyrrolidone K-30. Thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, particle size distribution by light scattering, solubility at different pHs, and dissolution profile experiments were carried out to evaluate the solid dispersions and physical mixtures. Results showed an increase in solubility, especially in acid medium, where the drug is protonated, and an enhancement in dissolution profiles, following first order kinetic, of solid dispersions manufactured by both the rotary evaporation and the spray-drying methods. Both methods proved to be equally adequate, when compared to physical mixtures. This is a consequence of particle size reduction, increased wettability due to intimate contact of the drug with the hydrophilic matrix, increased surface area, and the conversion of the crystalline to the amorphous state, which proved to be stable after 6 months at room temperature.

The purpose of this study is to compare the bioavailability of two itraconazole (CAS 84625-61-6) capsule formulations. An open, randomized, two-period crossover study with a 7-day washout interval was conduced in 32 healthy volunteers. The plasma samples were obtained up to 96 h after drug administration. A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of itraconazole in human plasma. Itraconazole and ketoconazole (internal standard) were extracted from the plasma by liquid-liquid extraction using diethylether : dichloromethane (70 : 30) as extraction solvent and separated on a C8 analytical column (150 mm x 4.6 mm I.D.) maintained at 40 degrees C. The elution was performed by a constant flow rate of 1.2 mL/min and the mobile phase consisted of acetonitrile and acetic acid 0.1% (85 :15 v/v). The mass spectrometer equipped with an electrospray source in positive mode, was set up in multiple reaction monitoring, to detect parent --> production 705.0 392.0 (itraconazole) and 531.0 --> 81.70 (ketoconazole). The chromatographic separation was obtained within 3.5 min and was linear in the concentration range of 5 to 600 ng/mL. Bioequivalence between the products was determined by calculating 90% confidence intervals for the ratio of C(max) (95.02%-109.48%), AUC(0-t) (81.41%-107.77%) and AUC(0-inf) (80.85%-106.86%). These values for the test and reference products are within the 80-125% interval, proposed by FDA and EMEA. It was concluded that the proposed method was successfully applied to a pharmacokinetic study in healthy human volunteers, and results showed that the two itraconazole formulations are bioequivalent in their rate and extent of absorption.

The objective of this work was to determine the contents of methylxanthines, caffeine and theobromine, and phenolic compounds, chlorogenic and caffeic acids, in 51 mate progenies (half-sib families) and estimate the heritability of genetic parameters. Mate progenies were from five Brazilian municipalities: Pinhão, Ivaí, Barão de Cotegipe, Quedas do Iguaçu, and Cascavel. The progenies were grown in the Ivaí locality. The contents of the compounds were obtained by high performance liquid chromatography (HPLC). The estimation of genetic parameters by the restricted maximum likelihood (REML) and the prediction of genotypic values via best linear unbiased prediction (BLUP) were obtained by the Selegen - REML/BLUP software. Caffeine (0.248-1.663%) and theobromine (0.106-0.807%) contents were significantly different (p0.5). The two different progeny groups determined for chlorogenic (1.365-2.281%) and caffeic (0.027-0.037%) acid contents were not significantly different (p

Mate (Ilex paraguariensis St. Hil) contains phytochemical compounds capable of preventing a number of health problems. Knowledge on the genetic contribution to the variability in these compounds can help to obtain mate progenies with higher levels thereof in breeding programs. The composition of triterpene saponins, methylxanthines, chlorogenic acid and the antioxidant activity of eight mate progenies were evaluated. Significant differences among progenies were verified in contents of triterpene saponins (0.003-0.080%), caffeine (0.226-1.377%), theobromine (0.176-0.831%), and chlorogenic acid (1.344-2.031%) and in antioxidant activity (31.251-51.406%). The contents of theobromine were found to be negatively correlated with saponins and caffeine, and caffeine with chlorogenic acid, while theobromine was positively correlated with chlorogenic acid. The heritability values for saponins (75.09%), caffeine (75.19%), theobromine (66.87%), chlorogenic acid (52.86%) and antioxidant activity (67.75%) indicate the possibility of genetic gain in selection for these traits.

Methylxanthines and phenolic compounds contents of 16 mate (Ilex paraguariensis St. Hil.) progenies from four Brazilian regions (Ivai, Quedas do Iguacu, Cascavel and Barao de Cotegipe) and those grown in three places within in the state of Parana (Ivai, Rio Azul and Guarapuava) were evaluated. Results revealed significant changes in total methylxanthines, caffeine and theobromine contents in progenies, according to their origin. Total methylxanthines (0.560-0.734%) and caffeine (0.490-0.611%) contents followed the order Ivai

Polyphenols from agroindustries byproducts have great potential as a source of antioxidant compounds. The present study evaluated the antioxidant activity and polyphenol content of the husks and seeds of grapes obtained from a winery of the produce wine. The hydroalcoholic extract (HAE) of the husks was obtained through an exhaustive maceration process. Seeds were extracted in a Soxhlet system, mixed with hydroalcoholic solution and the dried extract was partitioned into solvents to yield the chloroform fraction (CLF), ethyl acetate fraction (EAF), and butanol fraction (BUF). The EAF and HAE had phenolic equivalents of 200.76 and 320.64 mg of gallic acid per gram of extract, respectively. The HAE showed higher antioxidant activity than the fractions in the phosphomolybdenum method, the same in DPPH assay, with IC 50 of 16.82 mg/mL, and β -carotene/linoleate system, with antioxidant activity of 82.09%. High performance liquid chromatography (HPLC) method was developed and validated for quantifying trans -resveratrol in the HAE. The method showed linearity (2.5-7.5 µg/mL), correlation coefficient of 0.9907, precision and accuracy (resveratrol recovery = 101.02%). The HAE had a trans -resveratrol concentration of 17.33 µg/mg. The results of the validation of the HPLC method were satisfactory, which allowed analysis of the extract with precision and accuracy.

A sensitive and fast HPLC/MS/MS method for measurement of sufentanil and morphine in plasma was developed and validated. A single liquid-liquid extraction in alkaline medium was used for the cleanup of plasma, and fentanyl was added as an internal standard (IS). The analyses were carried out using a C18 column and the mobile phase acetonitrile-5 mM ammonium acetate + 0.25% formic acid (70 + 30, v/v). The triple-quadrupole mass spectrometer equipped with an electrospray source in positive mode was set up in the selective reaction monitoring mode to detect precursor --product ion transition 387.0238.0, 285.7165.1, and 337.0188.0 for sufentanil, morphine, and IS, respectively. The method was linear in the 0.05 (LOQ) - 500 ng/mL range for sufentanil and 10 (LOQ) - 1000 ng/mL range for morphine. Good selectivity, linearity, precision, accuracy, and robustness were obtained for the HPLC/MS/MS method. The proposed method was successfully applied for the determination of sufentanil and morphine in patients undergoing cardiac surgery.

This study was to evaluate and compare the pharmacokinetic and pharmacodynamic behavior of two formulations of furosemide (CAS 54-31-9) 40 mg tablets, administered as a single dose to healthy subjects. Plasma concentrations of furosemide were determined with a validated method by liquid chromatography coupled to mass spectrometry (LC-MS/MS). We obtained the parameters: AUC 0-t , AUC 0-∞ , K el , T 1/2 , C max e T max . The following parameters were determined in urine: Sodium, Potassium and Chlorine and the total volume. The 90% confidence intervals for the ratio of C max (93.63-121.92%), AUC 0–t (96.80-115.72%) and AUC 0-∞ (98.45-117.43%) respectively for test and reference. Statistical analysis of the similarity of the parameters for urinary volume, excretion of sodium, potassium and chlorine and assuming that both formulations reach the same plasma levels, we expect that the pharmacological effect is also the same. Whereas the rate and extent of absorption, both products can be considered therapeutic equivalents.

The purpose of this study is to compare the bioavailability of two itraconazole (CAS 84625-61-6) capsule formulations. An open, randomized, two-period crossover study with a 7-day washout interval was conduced in 32 healthy volunteers. The plasma samples were obtained up to 96 h after drug administration. A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of itraconazole in human plasma. Itraconazole and ketoconazole (internal standard) were extracted from the plasma by liquid-liquid extraction using diethylether : dichloromethane (70 : 30) as extraction solvent and separated on a C8 analytical column (150 mm x 4.6 mm I.D.) maintained at 40 degrees C. The elution was performed by a constant flow rate of 1.2 mL/min and the mobile phase consisted of acetonitrile and acetic acid 0.1% (85 :15 v/v). The mass spectrometer equipped with an electrospray source in positive mode, was set up in multiple reaction monitoring, to detect parent --production 705.0 392.0 (itraconazole) and 531.0 --81.70 (ketoconazole). The chromatographic separation was obtained within 3.5 min and was linear in the concentration range of 5 to 600 ng/mL. Bioequivalence between the products was determined by calculating 90% confidence intervals for the ratio of C(max) (95.02%-109.48%), AUC(0-t) (81.41%-107.77%) and AUC(0-inf) (80.85%-106.86%). These values for the test and reference products are within the 80-125% interval, proposed by FDA and EMEA. It was concluded that the proposed method was successfully applied to a pharmacokinetic study in healthy human volunteers, and results showed that the two itraconazole formulations are bioequivalent in their rate and extent of absorption.

O controle de qualidade tem um papel fundamental em todas as etapas da producao de um medicamento. A analise apropriada das materias-primas, dos produtos intermediarios e do produto acabado, associado ao controle adequado dos processos de producao, e essencial para que a qualidade do medicamento seja eficiente e seguro. Atualmente, muitos medicamentos genericos estao disponiveis no mercado brasileiro. Os processos envolvidos na producao dos mesmos buscam a qualidade total nas analises realizadas com o medicamento teste e com o medicamento referencia para provar a intercambialidade entre ambos. O presente trabalho teve por objetivo realizar estudo de equivalencia farmaceutica em tres apresentacoes de captopril. As analises realizadas foram identificacao, desintegracao, dissolucao, friabilidade, dureza, peso medio, uniformidade de conteudo, limite de dissulfeto de captopril e doseamento de acordo com a USP 25 e a Farmacopeia Brasileira 4a Edicao. Os resultados obtidos demonstraram que o medicamento teste captopril em tres apresentacoes apresentou-se equivalente ao medicamento referencia correspondente. 10.5216/ref.v5i1.4612

Mate (Ilex paraguariensis A. St.-Hil) is a native species of South America used to prepare traditional beverages. Recently a possible effect of its infusion on oxidative stress found in dyslipidemias has been reported. The main compounds related to these activities are phenolic compounds derived from chlorogenic acid. This study aimed to determine the anticholesteremic effect of the hydroethanolic extract (HEIP) and its n-butanolic fraction (n-BFIP), with standardized content of phenolic compounds derived from chlorogenic acid, in rats treated with high-fat diet (HFD). The contents of these compounds in the ethanol extract and n-butanol fraction were respectively two and three times higher than in traditional infusion with predominance of dicaffeoylquinic derivatives. The extracts were able to reduce serum triglycerides and cholesterol and decrease the atherogenic index in treated animals. These results support a potential effect of the mate extract in cardiovascular disease.

The objective of this work was to determine the contents of methylxanthines, caffeine and theobromine, and phenolic compounds, chlorogenic and caffeic acids, in 51 mate progenies (half?sib families) and estimate the heritability of genetic parameters. Mate progenies were from five Brazilian municipalities: Pinhão, Ivaí, Barão de Cotegipe, Quedas do Iguaçu, and Cascavel. The progenies were grown in the Ivaí locality. The contents of the compounds were obtained by high performance liquid chromatography (HPLC). The estimation of genetic parameters by the restricted maximum likelihood (REML) and the prediction of genotypic values via best linear unbiased prediction (BLUP) were obtained by the Selegen ? REML/BLUP software. Caffeine (0.248–1.663%) and theobromine (0.106–0.807%) contents were significantly different (p0.5). The two different progeny groups determined for chlorogenic (1.365–2.281%) and caffeic (0.027–0.037%) acid contents were not significantly different (p