SEMINAR ANNOUNCEMENT

PhD Thesis Defence Seminar
In Vitro and In Vivo Studies on Metabolic Drug Interactions with Warfarin in Rats

by

Ms Zhou Qingyu
Department of Pharmacy
National University of Singapore

on

Date: Tuesday, 13 May 2003
Time: 1100 - 1200 hrs
Venue: S4-05-10

Synopsis:

Warfarin, the most widely prescribed oral anticoagulant possessing a narrow therapeutic index, is subject to many drug interactions leading to serious consequences. The objectives of the present study were to (1) investigate the nature and quantitative elements of warfarin-drug interactions in rats, (2) predict human clearance values for warfarin enantiomers from in vitro metabolism data and animal data. The decreased hypoprothrombinaemic response to warfarin in rats in the presence of ubidecarenone was attributable to a significant increase in the total serum clearance values of warfarin enantiomers, in particular the R-enantiomer. 5-Fluorouracil co-administration decreased the total serum clearance value of S-warfarin that was associated with the augmentation of the anticoagulant effect of warfarin. Omeprazole did not affect the anticoagulant effect of warfarin and the total serum clearance values for warfarin enantiomers. Based on our in vitro metabolism data or in vivo rat data, together with the information retrieved from the literature, the magnitude of drug interactions with warfarin in man was quantitatively predicted.

Keywords: Warfarin enantiomers, drug interactions, pharmacokinetics, pharmacodynamics

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