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CYP2C9*3 and *13 alleles significantly affect the pharmacokinetics of irbesartan in healthy Korean subjects

  • Pharmacogenetics
  • Published:
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Abstract

Purpose

To evaluate the effects of two major polymorphisms of CYP2C9, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of irbesartan in healthy Korean volunteers.

Methods

A single 150-mg oral dose of irbesartan was given to 28 Korean volunteers, who had different CYP2C9 genotypes (12, 10, and 6 carriers of CYP2C9*1/*1, *1/*3, and *1/*13 genotypes respectively). Irbesartan levels were analyzed using HPLC fluorescence in plasma samples collected up to 36 h after the drug intake.

Results

Compared with CYP2C9*1 homozygous subjects, not only were the maximum plasma concentrations (Cmax) of irbesartan in CYP2C9*1/*3 and *1/*13 subjects 1.56- and 1.50-fold higher (P = 0.001), but the half-lives were also 1.38- and 1.50-fold longer (P = 0.001). The area under the plasma concentration–time curve (AUC) was 1.64- and 1.79-fold higher (P < 0.001). The oral clearance of irbesartan was 39.3% and 44.0% lower in the CYP2C9*1/*3 and *1/*13 subjects respectively, than in the *1/*1 subjects (P < 0.001). Likewise, the increases in half-life and decreases in oral clearance observed in CYP2C9*1/*13 individuals were similar to those in participants expressing the CYP2C9*1/*3 genotype.

Conclusions

CYP2C9 genetic polymorphisms markedly affected the pharmacokinetics of irbesartan in this study sample. The CYP2C9*3 and CYP2C9*13 alleles appear to be associated with the decreased metabolism of irbesartan.

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Acknowledgements

This study was supported by a grant from the Korean Food and Drug Administration. We thank Ho-Kyun Han, Kyeong-Joo Jeon, So-Jung Youn, Seul-Ki Keum, and Da-Hee Oh for their help with clinical study and subject genotyping.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea

    Chang-Ik Choi, Mi-Jeong Kim, Eun-Kyung Chung, Hye-In Lee, Choon-Gon Jang, Jung-Woo Bae & Seok-Yong Lee

  2. College of Pharmacy, Keimyung University, Daegu, 704-701, Republic of Korea

    Jung-Woo Bae

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  1. Chang-Ik Choi
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  2. Mi-Jeong Kim
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Correspondence to Jung-Woo Bae or Seok-Yong Lee.

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Chang-Ik Choi and Mi-Jeong Kim contributed equally to this article.

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Choi, CI., Kim, MJ., Chung, EK. et al. CYP2C9*3 and *13 alleles significantly affect the pharmacokinetics of irbesartan in healthy Korean subjects. Eur J Clin Pharmacol 68, 149–154 (2012). https://doi.org/10.1007/s00228-011-1098-0

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  • DOI: https://doi.org/10.1007/s00228-011-1098-0

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