Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers.
OBJECTIVE
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), 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 concentration was 15.1 ng ml(-1), t(1/2) 5.6 h, AUC(0,infinity) 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.
Kees
F
F
Department of Pharmacology, University of Regensburg, Germany. frieder.kees@chemie.uni-regensburg.de
Färber
L
L
Bucher
M
M
Mair
G
G
Mörike
K
K
Grobecker
H
H
D000284:Administration, Oral; D000328:Adult; D000932:Antiemetics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D013034:Sparteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000652:urine; D000077526:Tropisetron
D000932:Antiemetics; D007211:Indoles; C044693:5-dehydrosparteine; D013034:Sparteine; C044694:2-dehydrosparteine; D000077526:Tropisetron; D019389:Cytochrome P-450 CYP2D6