Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers

Aims To establish the bioavailability of tropisetron (5 mg) administered or ally as capsule compared with 2 mg given intravenously. Methods Using a randomized crossover design, 18 healthy volunteers received a single oral dose of tropisetron (5 mg) and an intravenous bolus of tropi setron (2 mg) separated by a wash-out period of 1 week. Plasma concentratio ns of tropisetron were determined by h.p.l.c. and the pharmacokinetic param eters were estimated. Results The mean pharmacokinetic parameters for 5 mg tropisetron given oral ly were C-max 3.46 ng ml(-1), t(max) 2.6 h, t(1/2) 5.7 h and AUC(0,infinity ) 32.9 ng ml(-1) h. After intravenous administration initial plasma concent ration was 15.1 ng ml(-1) t(1/2) 5.6 h, AUC(0,infinity) 20.7 ng ml(-1) h, V 678 1 and CL 1800 ml min(-1). An inverse correlation was demonstrated betw een CYP2D6 activity, measured by the sparteine metabolic ratio, and the bio availability (mean 0.60, range 0.27-0.99) of oral tropisetron. Conclusions Tropisetron exhibits a wide range of oral bioavailability at th erapeutic doses, which is mainly determined by CYP2D6 activity.