Acta Pharmacologica Sinica (2009) 30: 478-484; doi: 10.1038/aps.2009.27

Aim: To evaluate the potential drug-drug interactions between bifendate and cyclosporine, a substrate of CYP 3A 4, in relation to different CYP 3A 4*18B genotype groups.  

Methods: To evaluate the potential drug-drug interactions between bifendate and cyclosporine, a substrate of CYP 3A 4, in relation to different CYP 3A 4*18B genotype groups. 

Results: After the treatment with bifendate, the areas under the curve (AUC_0-4 and AUC_0-∞) decreased significantly by 9.7%±3.7% (P=0.01) and 19.2%±16.8% (P=0.001) in CYP 3A 4*1/*1 subjects, 11.3%±9.4% (P=0.03) and 10.5%±9.6% (P=0.043) in CYP 3A 4*1/*18B subjects, and 40.2%±14.7% (P=0.02) and 37.5%±15.8% (P=0.003) in CYP 3A 4*18B/*18B subjects.  Meanwhile, the decreases in the AUC_0-4 and AUC_0-∞ values in the three groups were significantly different (using one-way analysis of variance, P=0.001 and P=0.001), and the change in the CYP 3A 4*18B/*18B group was greater than that in the other two groups.  The oral clearance of cyclosporine was altered in all the subjects, with substantial increases by 10.2%±4.4% (P=0.004) in CYP 3A 4*1/*1 subjects, 14.0%±12.0% (P=0.048) in CYP 3A 4*1/*18B subjects, and 32.4%±21.7% (P=0.013) in CYP 3A 4*18B/*18B subjects.   

Keywords: bifendate; cyclosporine; pharmacokinetics; CYP 3A 4*18B