CYP2C11 is the most abundant isoform of cytochrome P450s (CYPs) in male rats and is considered the main enzyme for warfarin metabolism. 2. To further access the function of CYP2C11 in warfarin metabolism and efficacy, a -null rat model was used to study warfarin metabolism with both and approaches. Prothrombin time (PT) of warfarin was also determined. 3. The maximum rate of metabolism (V) and intrinsic clearance (CL) of liver microsomes from -null males were reduced by 37 and 64%, respectively, compared to those in Sprague Dawley (S-D) rats. The K of liver microsomes from -null males was increased by 73% compared to that of S-D rats. The time to reach the maximum plasma concentration (T) of warfarin in -null males was significantly delayed compared to that in S-D males, and the CL rate was also reduced. The PT of -null rats was moderately longer than that of S-D rats. 4. In conclusion, the clearance rate of warfarin was mildly decreased and its anticoagulant effect was moderately increased in male rats following gene knockout. CYP2C11 played a certain role in the clearance and efficacy of warfarin, while it did not seem to be essential.
