Inhibition of S-warfarin metabolism by nonsteroidal antiinflammatory drugs in human liver microsomes in vitro.

We studied the inhibition of S-warfarin metabolism by nonsteroidal antiinflammatory drugs (NSAIDs) in human liver microsomes in vitro. After screening for potential inhibitors among ten NSAIDs using human recombinant cytochrome P450, inhibition kinetic parameters were estimated using human liver microsomes. Phenylbutazone and bucolome were suggested to increase the unbound steady-state level of S-warfarin about four- and five-fold, respectively, as estimated from these metabolic parameters.