Omeprazole-induced acute interstitial nephritis is not related to CYP2C19 genotype or CYP2C19 phenotype.
OBJECTIVE
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.
Helsby
Nuala A
NA
Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
Lo
Wing-Yee
WY
Simpson
Ian J
IJ
Voss
David M
DM
Logan
Kaye E
KE
Searle
Martin
M
Schollum
John B W
JB
de Zoysa
Janak R
JR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000139:chemically induced*; D009853:Omeprazole / Q000009:adverse effects*; D010641:Phenotype; D054328:Proton Pump Inhibitors / Q000009:adverse effects*
D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole