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Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S ‐mephenytoin 4′‐hydroxylation phenotype and genotype *
Author(s) -
Tanaka Makoto,
Ohkubo Tadashi,
Otani Koichi,
Suzuki Akihito,
Kaneko Sunao,
Sugawara Kazunobu,
Ryokawa Yuichi,
Hakusui Hideo,
Yamamori Shunji,
Ishizaki Takashi
Publication year - 1997
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(97)90081-3
Subject(s) - mephenytoin , pantoprazole , cyp2c19 , pharmacogenetics , pharmacokinetics , pharmacology , metabolite , chemistry , debrisoquine , medicine , genotype , omeprazole , metabolism , biology , cytochrome p450 , biochemistry , gene
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 (t ½ ), 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 log 10 % urinary excretion of 4′‐hydroxymephenytoin and AUC of pantoprazole ( r S = −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). Clinical Pharmacology & Therapeutics (1997) 62 , 619–628; doi: