학술논문
Influence of taranabant, a cannabinoid-1 receptor inverse agonist, on pharmacokinetics and pharmacodynamics of warfarin
Document Type
Report
Author
Source
Advances in Therapy. Nov, 2008, Vol. 25 Issue 11, p1175, 16 p.
Subject
Language
English
ISSN
0741-238X
Abstract
Introduction The pharmacokinetic/pharmacodynamic effects of warfarin were assessed in the presence and absence of taranabant, an orally active, highly selective, potent, cannabinoid-1 receptor inverse agonist, which was being developed for the treatment of obesity. Methods Twelve subjects were assigned to two open-label treatments in fixed sequence separated by a 14-day washout. Treatment A was single-dose warfarin 30 mg on day 1. Treatment B was multiple-dose taranabant 6 mg each day for 21 days (days -14 to day 7) with coadministration of singledose warfarin 30 mg on day 1. Blood samples were collected predose and up to 168 hours postdose for assay of R(+)-and S(-)-warfarin and prothrombin time/international normalized ratio (PT/INR). Results The geometric mean ratios (GMR warfarin+taranabant/warfarin 90% confidence interval [CI] primary endpoints) for area under the curve (AUC).sub.0-[infinity] for R(+)-and S(-)-warfarin were 1.10 (90% CI: 1.03, 1.18) and 1.06 (90% CI: 1.00, 1.13), respectively. The GMRs (warfarin+taranabant/warfarin) for the maximum plasma concentration (C.sub.max) of S(-)-and R(+)-warfarin were 1.16 (90% CI: 1.05, 1.28) and 1.17 (90% CI: 1.07, 1.29), respectively. For R(+)-and S(-)-warfarin, the 90% CIs for AUC.sub.0-[infinity] GMRs fell within the prespecified bounds. Taranabant did not produce a clinically meaningful effect on PT/INR. Conclusion No clinically significant alterations of the pharmacokinetics of R(+)-and S(-)-warfarin were seen following coadministration of multipledose taranabant 6 mg and single-dose warfarin 30 mg.