Omeprazole-induced acute interstitial nephritis is not related to CYP2C19 genotype or CYP2C19 phenotype

被引:12
作者
Helsby, Nuala A. [2 ]
Lo, Wing-Yee [2 ]
Simpson, Ian J. [3 ,4 ]
Voss, David M. [4 ,5 ]
Logan, Kaye E. [6 ]
Searle, Martin [6 ]
Schollum, John B. W. [7 ]
de Zoysa, Janak R. [1 ,3 ]
机构
[1] N Shore Hosp, Dept Med, N Shore City, New Zealand
[2] Univ Auckland, Dept Mol Med & Pathol, Auckland 1, New Zealand
[3] Auckland City Hosp, Dept Renal Med, Auckland, New Zealand
[4] Univ Auckland, Dept Med, Auckland, New Zealand
[5] Middlemore Hosp, Dept Nephrol, Manakau City, New Zealand
[6] Christchurch Hosp, Dept Nephrol, Christchurch, New Zealand
[7] Dunedin Publ Hosp, Dept Nephrol, Dunedin, New Zealand
关键词
acute interstitial nephritis; CYP2C19; genotype; omeprazole; PROTON PUMP INHIBITORS; PHARMACOKINETICS; POLYMORPHISM; METABOLISM;
D O I
10.1111/j.1365-2125.2010.03623.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
AIM Omeprazole-induced acute interstitial nephritis (OIAIN) is a rare adverse event. It is unknown if this is an idiosyncratic immune mediated reaction or if it relates to direct drug toxicity. Individuals who are homozygous for the variant alleles of CYP2C19 are poor metabolizers of omeprazole and have a greater exposure to the drug. The aim of this study was to determine the prevalence of the CYP2C19 poor metabolizer genotype and phenotype in patients with OIAIN. METHODS Twenty patients were genotyped for the CYP2C19 variant alleles 681G>A and *3, 636G>A) by RFLP-PCR analysis and eighteen phenotyped for CYP2C19 metabolizer status. RESULTS The frequency of the CYP2C19*2 allelic variant was 12.5%, no *3 allelic variants were detected and no patient was a homozygous variant genotype. This was not different from the expected frequency. 33% of subjects were phenotypically CYP2C19 poor metabolizers. CONCLUSIONS There was discordance between CYP2C19 genotype and phenotype. However, up to 45% of healthy elderly subjects have a poor metabolizer phenotype. Thus neither CYP2C19 poor metabolizer genotype nor phenotype is a risk factor for OIAIN.
引用
收藏
页码:516 / 519
页数:4
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