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• W2040372778 abstract "Objectives and methods We assessed the relationship between the metabolism of R- and S-mephobarbital (MPB) and genetic polymorphisms of cytochrome P450 (CYP) 2C19 and CYP2B6. Nine homozygous extensive metabolizers (homo-EMs, 2C19*1/2C19*1) of CYP2C19, ten heterozygous EMs (hetero-EMs, 2C19*1/2C19*2, 2C19*1/2C19*3) and eleven poor metabolizers (PMs, 2C19*2/2C19*2, 2C19*3/2C19*3, 2C19*2/2C19*3) recruited from a Japanese population, received an oral 200 mg-dose of racemic MPB. Blood and urine samples were collected, and R-MPB, S-MPB and the metabolites, phenobarbital (PB) and 4′-hydroxy-MPB, were measured. Each subject was also genotyped for CYP2B6 gene. Results The mean area under the plasma concentration–time curve (AUC) of R-MPB was 92-fold greater in PMs than in homo-EMs. R/S ratios for AUC of MPB were much higher in PMs than in EMs (homo- and hetero-). The cumulative urinary excretion of 4′-hydroxy-MPB up to 24 h postdose was 21-fold less in PMs than in homo-EMs. The metabolic ratio of AUCPB/(AUCS−MPB + AUCR−MPB) was higher in PMs than in EMs (homo- and hetero-). In addition, this metabolic ratio was lower in the carriers of CYP2B6*6 compared with that in its non-carriers. Conclusions Our results indicate that the 4′-hydroxylation of R-MPB is mediated via CYP2C19 and that the rapid 4′-hydroxylation of R-MPB results in a marked difference in the pharmacokinetic profiles between R-MPB and S-MPB in the different CYP2C19 genotypic individuals. In addition, a minor fraction of the interindividual variability in PB formation from MPB may be explainable by the CYP2B6*6 allele." @default.
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• W2040372778 date "2004-08-01" @default.
• W2040372778 modified "2023-10-10" @default.
• W2040372778 title "Pharmacogenetic roles of CYP2C19 and CYP2B6 in the metabolism of R- and S-mephobarbital in humans" @default.
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• W2040372778 doi "https://doi.org/10.1097/01.fpc.0000114764.78957.22" @default.
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