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Clin Pharmacol Ther. 1997 Dec;62(6):619-28.

Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S-mephenytoin 4'-hydroxylation phenotype and genotype.

Author information

1
Drug Metabolism and Analytical Chemistry Research Laboratory, Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan.

Abstract

OBJECTIVES:

To assess the possible relationship between the metabolic disposition of pantoprazole and genetically determined S-mephenytoin 4'-hydroxylation phenotype and genotype.

METHODS:

The pharmacokinetic disposition of pantoprazole was investigated in 14 Japanese male volunteers (seven extensive and seven poor metabolizers of S-mephenytoin). All subjects received a single 40 mg oral dose of pantoprazole as the enteric-coated formulation.

RESULTS:

An interphenotypic difference in the metabolic disposition of pantoprazole was observed: the mean values for area under the concentration-time curve (AUC), elimination half-life (t1/2), and apparent oral clearance were significantly (p < 0.01) greater, longer, and lower, respectively, in the poor metabolizers than in the extensive metabolizers. The mean AUC of pantoprazole sulfone was greater (p < 0.01) in the poor metabolizers than in the extensive metabolizers, whereas the mean AUC of the main demethylated metabolite (M2) was lower (p < 0.01) in the poor metabolizers than in the extensive metabolizers. A significant negative correlation was observed between the individual values for log10% urinary excretion of 4'-hydroxymephenytoin and AUC of pantoprazole (rs = -0.816; p < 0.005). The CYP2C19 genotyping test results were found to be in a complete accordance with the phenotypes.

CONCLUSION:

These data indicated that the metabolic disposition of pantoprazole is under the pharmacogenetic control of S-mephenytoin 4'-hydroxylase (CYP2C19).

PMID:
9433390
DOI:
10.1016/S0009-9236(97)90081-3
[Indexed for MEDLINE]

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