Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers

Abstract

Aims: To establish the bioavailability of tropisetron (5 mg) administered orally 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 tropisetron (2 mg) separated by a wash-out period of 1 week. Plasma concentrations of tropisetron were determined by h.p.l.c. and the pharmacokinetic parameters were estimated. Results: The mean pharmacokinetic parameters for 5 mg tropisetron given orally were Cmax 3.46 ng ml-1, tmax 2.6 h, t1/2 5.7 h and AUC(0,∞) 32.9 ng ml-1 h. After intravenous administration initial plasma concentration was 15.1 ng ml-1, t1/2 5.6 h, AUC(0,∞) 20.7 ng ml-1 h, V 678 l and CL 1800 ml min-1. An inverse correlation was demonstrated between CYP2D6 activity, measured by the sparteine metabolic ratio, and the bioavailability (mean 0.60, range 0.27-0.99) of oral tropisetron. Conclusions: Tropisetron exhibits a wide range of oral bioavailability at therapeutic doses, which is mainly determined by CYP2D6 activity.