@article{APS6617,
author = {Yong Zeng and Yi-jing He and Fu-yuan He and Lan Fan and Hong-hao Zhou},
title = {Effect of bifendate on the pharmacokinetics of cyclosporine in relation to the CYP3A4 * 18B genotype in healthy subjects},
journal = {Acta Pharmacologica Sinica},
volume = {30},
number = {4},
year = {2016},
keywords = {},
abstract = {Aim: To evaluate the potential drug-drug interactions between bifendate and cyclosporine, a substrate of CYP3A4, in relation to different CYP3A4*18B genotype groups.
Methods: Eighteen unrelated healthy subjects (six CYP3A4*1*1, six CYP3A4*1/*18B, and six CYP3A4*18/*18B) were selected for this study. After repeated oral administration of a placebo or bifendate (three times daily for 14 d), the whole-blood level of cyclosporine was measured using high performance liquid chromatography-electrospray mass spectrometry (HPLC/ESI-MS). This study was carried out in a two-phase randomized crossover manner.
Results: After the treatment with bifendate, the areas under the curve (AUC0–24 and AUC0–∞) decreased significantly by 9.7%±3.7% (P=0.01) and 19.2%±16.8% (P=0.001) in CYP3A4*1/*1 subjects, 11.3%±9.4%(P=0.03) and 10.5%±9.6% (P=0.043) in CYP3A4*1/*18B subjects, and 40.2%±14.7% (P=0.02) and 37.5%±15.8% (P=0.003) in CYP3A4*18B/*18B subjects. Meanwhile, the decreases in the AUC0–24 and AUC0–∞ 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 CYP3A4*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 CYP3A4*1/*1 subjects, 14.0%±12.0% (P=0.048) in CYP3A4*1/*18B subjects, and 32.4%±21.7% (P=0.013) in CYP3A4*18B/*18B subjects.
Conclusion: These results suggest that bifendate decreases the plasma concentration of cyclosporine in a CYP3A4 genotype-dependent manner.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/6617}
}