RESUMO
A high-performance liquid chromatographic method has been developed for the determination of tolbutamide and its metabolites in human plasma and urine. The compounds examined were extracted with diethyl ether from the acidified biological fluid. Chlorpropamide was used as internal standard, and 235 nm was chosen as the wavelength for diode-array detection. A study of the relationship between the capacity factor and the mobile phase composition and pH showed that acetonitrile-2-propanol-0.1% orthophosphoric acid (17: 17: 66, v/v) was the best eluent on a C8 reversed-phase column. The method is precise, sensitive and suitable for pharmacological investigations.
Assuntos
Tolbutamida/metabolismo , Cromatografia Líquida de Alta Pressão , Humanos , Concentração de Íons de Hidrogênio , Espectrofotometria Ultravioleta , Tolbutamida/sangue , Tolbutamida/urinaAssuntos
Antipirina/farmacocinética , Glucagon/administração & dosagem , Salicilatos/farmacocinética , Adulto , Digestão/efeitos dos fármacos , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Glucagon/farmacologia , Humanos , Infusões Parenterais , Absorção Intestinal/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Ácido SalicílicoRESUMO
The relationship between acetylator phenotype and the inhibitory effect of cimetidine on the hepatic metabolism of antipyrine has been studied in 20 subjects. Cimetidine, 1,0 g/day resulted in a significant decrease in the metabolic clearance rate of antipyrine, but only in slow acetylators, as fast acetylators were less affected. No sex difference was observed. No major change occurred in the urinary excretion of D-glucaric acid, which means that cimetidine had not-affected that Phase II reaction. It did significantly decrease the urinary partial clearance rate of norantipyrine, leaving that of antipyrine and 4-OH-antipyrine unchanged, which suggests that cimetidine had preferentially inhibited the P450 isozyme that catalyses norantipyrine formation.