CYP2C9 Polymorphism is not a Major Determinant of Bosentan Exposure in Healthy Volunteers

摘要

In their recent article, "Association of CYP2C9*2 With Bosentan-Induced Liver Injury,"1 Markova et al. report a study in which they assessed the relationships of polymorphisms in cytochrome P450 2C9 (CYP2C9), adenosine triphosphate (ATP)-binding cassette members Bll and C2 (ABCB11 and ABCC2), and organic anion-trans-porting polypeptide IB (OATP1B) with hepatotoxicity during bosentan treatment, and the only associated polymorphic allele was CYP2C9*2. In their in vitro analysis of bosentan metabolism, CYP2C9*3 was less active than *2, and both were less active than the wild-type cytochrome, suggesting that bosentan accumulates in these patients and causes hepatotoxicity.