ABSTRACT
OBJETIVO: Comparar a biodisponibilidade de duas formulações de glimepirida em 26 voluntários sadios de ambos os sexos. MATERIAL E MÉTODOS: O estudo foi aberto, cruzado e randomizado com dois períodos e wash out de 14 dias. As amostras foram obtidas em um intervalo de 48 horas. As concentrações de glimepirida foram analisadas por HPLC MS/MS. Das curvas de concentração de glimepirida no plasma versus tempo, foram obtidos os seguintes parâmetros farmacocinéticos: ASC(0-t), ASC(0-∞), Cmax, Ke, Tmax e T1/2. RESULTADOS: A razão entre as média geométricas de Glimepirida/Amaryl® 4 mg foi de 102,35 por cento para ASC(0-t); 102,35 por cento para ASC(0-∞) e 99,31 por cento para Cmax. Os intervalos de confiança de 90 por cento (IC 90 por cento) foram de 92,62-109,55 por cento; 95,62-109,55 por cento e 88,60-111,32 por cento, respectivamente. CONCLUSÃO: Como o IC 90 por cento para Cmax, ASC(0-t) e ASC(0-∞) estava dentro do intervalo de 80-125 por cento, concluiu-se que ambas as formulações foram bioequivalentes de acordo com o grau e a extensão de sua absorção.
OBJECTIVE: To compare the bioavailability of two glimepiride 4-mg tablet formulation in 26 healthy volunteers of both sexes. MATERIAL AND METHODS: The study was conducted open with randomized two-period crossover design and a 14-day washout period. Samples were obtained over a 48-hour interval. Glimepiride concentrations were analyzed by LC-MS-MS. From the glimepiride plasma concentration versus time curves the following pharmacokinetic parameters were obtained: AUC(0-last), AUC(0-t), AUC(0-∞), Ke, T1/2, Cmax, and Tmax. RESULTS: Geometric mean of Glimepirida/Amaryl® 4 mg was 102.35 percent for AUC(0-t), 102.35 percent for AUC(0-∞) and 99.31 percent for Cmax. The 90 percent CI was 92.62-109.55 percent; 95.62-109.55 percent e 88.60-111.32 percent, respectively. CONCLUSION: Since the 90 percent CI for both Cmax, AUC(0-t), and AUC(0-∞) were within the interval of 80-125 percent, it was concluded that both formulations were bioequivalent, according to both the rate and extent of absorption.
Subject(s)
Adult , Female , Humans , Male , Hypoglycemic Agents/pharmacokinetics , Sulfonylurea Compounds/pharmacokinetics , Biological Availability , Capsules , Cross-Over Studies , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/blood , Reference Values , Sulfonylurea Compounds/administration & dosage , Sulfonylurea Compounds/blood , Therapeutic EquivalencyABSTRACT
A high-performance liquid chromatographic [HPLC] method has been developed for the simultaneous analysis of three frequently used sulfonylureas [chlorpropamide, glipizide and glibenclamide] by using a reversed phase C-8 column with a mobile phase consisting of 0.1% Ortho- phosphoric acid pH 2.7: isopropanol: acetonitrile, [45:25:30] operated at ambient temperature, with analysis time less than ten minutes. The eluted drugs were monitored by UV at 235nm. The extraction was performed by using dichloromethane after the plasma sample was mixed with the buffer [0.1% orthophosphoric acid].The overall recoveries and relative standard deviations were [93.7 +/- 5.3]% for chlorpropamide, [91.5 +/- 4.9]% for glipizide and [95 +/- 2.8]% for glibenclamide. The response was linear in the range [0.1 -100mg/ml] for chlorpropamide, glipizide, and glibenclamide, with r' > 0.999 for all drugs. Detection limits were 2ng/ml plasma for chlorpropamide, 15ng/ml plasma for glipizide and 7ng/ml plasma for glibenclamide, measured at a Signal/ Noise [S/N] of 3. No interference from administered drugs [barbiturates, b-blockers, Tranquillizer, Antihypertensive, Histamine antagonist, Antidepressant, anti emetic, and anticonvulsant] or endogenous constituents were observed