The contribution of the enzymes CYP2D6 and CYP2C19 in the demethylation of artemether in healthy subjects.

摘要: The contribution of the enzymes CYP2D6 and CYP2C19 to metabolism artemether was evaluated in a cross-over study seven healthy adult Caucasian subjects. pharmacokinetic properties its active metabolite dihydroartemisinin were compared when given 100 mg orally alone or combination with either CYP2D6-inhibitor quinidine CYP2C19-inhibitor omeprazole. Plasma concentrations measured reversed phase high performance liquid chromatography electro-chemical detection (HPLC-ED). Artemether rapidly absorbed mean tmax 0.8 h (95% confidence interval, CI=0.5–1.1) reaching Cmax 29 ng/ml (14–45 ng/ml). elimination half-life 1.3 (0.8–1.8 h). parameters for not significantly different from those artemether. combined revealed no significant changes plasma dihydroartemisinin. No seen omeprazole as inhibitor. A second peak concentration profile observed 2–4 after drug intake. This phenomenon possibly related variable gastric emptying. major found metabolism. interethnic differences on basis genetic polymorphism these is be expected.