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Xenobiotica
the fate of foreign compounds in biological systems
Volume 39, 2009 - Issue 10
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Research Article

Effects of the CYP2C9*13 allele on the pharmacokinetics of losartan in healthy male subjects

Z. LiPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
G. WangPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
L.-S. WangPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
W. ZhangPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
Z.-R. TanPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
L. FanPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
B.-L. ChenPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
Q. LiPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
J. LiuPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
J.-H. TuPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
D.-L. HuPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
,
Z.-Q. LiuPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. China
&
H.-H. ZhouPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, P. R. ChinaCorrespondence[email protected]
 show all
Pages 788-793 | Received 27 Apr 2009, Accepted 22 Jun 2009, Published online: 15 Jul 2009
 
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Abstract

  1. The aim of the study was to determine the pharmacokinetics of losartan in relation to the CYP2C9*13 allele.

  2. A single oral dose of 50 mg losartan was administrated to each of the 16 healthy male volunteers with a different genotype (CYP2C9*1/*1, n = 6; CYP2C9*1/*13, n = 4; and CYP2C9*1/*3, n = 6). Blood samples were collected from pre-dose up to 24 h after the drug administration. Plasma losartan and E3174 (an active metabolite of losartan) were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

  3. All the subjects finished the study without adverse drug effects. In the present study, the frequencies of CYP2C9*13 and *13 alleles were 0.6% and 2.6% in Chinese healthy volunteers, respectively, and both alleles were in Hardy–Weinberg equilibrium. Compared with the subjects in the CYP2C9*1/*1 group, individuals carrying the CYP2C9*1/*13 genotype showed significantly a longer t1/2 of losartan and E3174 and markedly increased the area under the curve (AUC) of losartan. Meanwhile, the CYP2C9*1/*3 genotype group had significant differences in t1/2 and Cmax of E3174 compared with the CYP2C9*1/*1 group. The ratio of AUCE3174/AUClosartan after losartan administration in the CYP2C9*1/*13 and CYP2C9*1/*3 groups was also statistically different from that in the CYP2C9*1/*1 group.

  4. The data indicate that the presence of the CYP2C9*13 allele results in poor metabolism of losartan after a single oral dose.

Acknowledgements

This work was supported by research grants from the National Natural Science Foundation of China (Grant Numbers 30000211, 30200346, and 30472054), by the China Medical Board of New York (Grant Number 01-755), and by the Postdoctoral Science Foundation of Central South University.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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