Effect of 36 CYP2C9 variants found in the Chinese population on losartan metabolism in vitro. (March 2014)

• Record Type: Journal Article
• Authors: Wang, Yu-Han; Pan, Pei-Pei; Dai, Da-Peng; Wang, Shuang-Hu; Geng, Pei-Wu; Cai, Jian-Ping; Hu, Guo-Xin
• Is Part Of: Xenobiotica. Volume 44:Number 3(2014:Mar.)
• Page Start: 270
• Page End: 275
• Publication Date: 2014-03
• Subjects: Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2013.820007
• Languages: English
• ISSNs: 0049-8254

Abstract

<abstract> <title>Abstract</title> <p>1. <?ri?>CYP2C9 is an important member of the cytochrome P450 enzyme superfamily, with 57 CYP2C9 allelic variants being previously reported. Among these variants, we recently identified 21 novel alleles (<italic>*36–*56</italic>) in the Han Chinese population. The aim of this study was to assess the catalytic activities of 36 CYP2C9 variants found in the Chinese population toward losartan <italic>in vitro</italic>.</p> <p>2. <?ri?>Insect microsomes expressing the 36 CYP2C9 variants were incubated with 0.5–25 μM losartan for 30 min at 37 °C. Next, the products were extracted, and signal detection was performed using high-performance liquid chromatography.</p> <p>3. <?ri?>Compared with wild-type CYP2C9.1, the intrinsic clearance (<italic>V</italic>_max<italic>/K_m</italic>) values of all variants except for CYP2C9.56 were significantly altered. One variant exhibited markedly increased values (&gt;250%), whereas 33 variants exhibited significantly decreased values (from 20 to 96%) due to increased <italic>K_m</italic> and/or decreased V_max values.</p> <p>4. <?ri?>These findings suggest that more attention should be paid to subjects carrying these infrequent <italic>CYP2C9</italic> alleles when administering losartan in the clinic.</p> </abstract>