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

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Omeprazole‐induced acute interstitial nephritis (OIAIN) is a rare adverse drug reaction. It is typically considered to be an idiosyncratic reaction affecting elderly patients. Omeprazole is a substrate for CYP2C19 and individuals who are homozygous variant for the null allele are poor metabolizers of this drug. These individuals have higher exposure to omeprazole. In the elderly metabolism of omeprazole is reported to be decreased despite a ‘normal activity’ genotype. WHAT THIS PAPER ADDS • The CYP2C19 poor metabolizer genotype was not over represented in patients with OIAIN. However, almost a third of the patients appeared to have deficient CYP2C19 function. • Metabolism of omeprazole may be compromised in the elderly and caution should be exercised when using this medication in this group of patients. 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 (*2, 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.

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