Rifampicin treatment greatly increases the apparent oral clearance of quinidine

We investigated the effect of cytochrome P450 induction by rifampicin on th e in vivo oxidative metabolism of quinidine. The pharmacokinetics of a 200 mg oral single dose quinidine were studied before and after one week of dai ly treatment with 600 mg rifampicin in six healthy young male volunteers. B iomarker reactions of cytochrome P450 isozyme activities in the form of caf feine, sparteine, mephenytoin, tolbutamide and cortisol metabolism were app lied. The median total apparent oral clearance and partial clearance by 3-h ydroxylation of quinidine increased 9 times. The partial clearance by N-oxi dation increased 6 times. The C-max and the elimination half life were redu ced 3 times. No statistically significant changes were found for quinidine t(max) and renal clearance. The cortisol metabolic ratio increased 5 times, while no statistically significant effects were seen for other CYP marker reactions. The results indicate that the inductive effect of rifampicin is likely to be of clinical relevance particulary when used concomitantly with drugs metabolized by CYP3A4.