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.