Prediction of the impact of CYP2C9 and VKORC1 genotypes on warfarin-sorafenib interactions in whites and Asians.

ABSTRACT

Aim: To predict the impact of the different CYP2C9 and VKORC1 genotypes on warfarin-sorafenib interactions in whites and Asians. Materials & methods: The influences of the CYP2C9*1/*3 and VKORC1 -1639 A/A genotypes on increases in anticoagulation responses (international normalized ratio [INR]) in the presence of sorafenib were predicted using the population pharmacokinetic/pharmacodynamic (PK/PD) model in whites and Asians. Results: INRs were predicted to be 2.0-2.1- versus 1.8-1.9-times higher in the presence of sorafenib in the CYP2C9 (*1/*1 vs *1/*3) groups than those for warfarin alone in both whites and Asians. INRs were also predicted to be 2.1-2.2- versus 1.9-2.1-times higher in the VKORC1 (GG or GA vs AA) groups. Conclusion: Warfarin-sorafenib interactions might be similar irrespective of CYP2C9 and VKORC1 genotypes or ethnicity.