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 ant iinflammatory drugs (NSAIDs) in human liver microsomes in vitro. After screening for potential inhibitors among ten NSAIDs using human recom binant cytochrome P450, inhibition kinetic parameters were estimated u sing human liver microsomes. Phenylbutazone and bucolome were suggeste d to increase the unbound steady-state level of S-warfarin about four- and five-fold, respectively, as estimated from these metabolic paramet ers.