Abstract
Objective
The purpose of this study was to elucidate the pharmacokinetics of each enantiomer of lansoprazole and 5-hydroxylansoprazole in three different CYP2C19 genotype groups of Japanese subjects.
Methods
Healthy subjects (n=18), of whom 6 were homozygous extensive metabolizers (homEMs), 6 were heterozygous extensive metabolizers (hetEMs) and 6 were poor metabolizers (PMs), participated in the study. After a single oral dose of 60 mg of racemic lansoprazole, the plasma concentrations of the lansoprazole enantiomers, 5-hydroxylansoprazole enantiomers and lansoprazole sulfone were measured for 24 h post-dose.
Results
The plasma concentrations of (R)-lansoprazole were remarkably higher in all three CYP2C19 genotype groups than those of the corresponding (S)-enantiomer. The mean maximum plasma concentration (C max) of (S)-lansoprazole differed significantly among the three groups, whereas there was no difference for the (R)-enantiomer. The relative area under the plasma concentration (AUC) ratios of (R)- and (S)-lansoprazole in the homEMs, hetEMs, and PMs were 1:1.5:4.0 and 1:1.8:7.4, respectively. Yet, the relative AUC ratios of 5-hydroxylansoprazole to lansoprazole for the (R)- and (S)-enantiomers in the homEMs, hetEMs, and PMs were almost the same (1:0.73:0.12 and 1:0.77:0.13, respectively). However, the AUC ratios of the (S)-enantiomer were 13-fold greater for the three CYP2C19 genotypes than those of the corresponding (R)-enantiomer.
Conclusions
The magnitude of the contribution of CYP2C19 to the 5-hydroxylation of (S)-lansoprazole was greater than that of the (R)-enantiomer. The R/S ratios for the AUC of lansoprazole for the homEMs, hetEMs and PMs were 12.7, 8.5 and 5.8, respectively, suggesting a significant effect of CYP2C19 polymorphisms on the stereoselective disposition of lansoprazole.
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Miura, M., Tada, H., Yasui-Furukori, N. et al. Pharmacokinetic differences between the enantiomers of lansoprazole and its metabolite, 5-hydroxylansoprazole, in relation to CYP2C19 genotypes. Eur J Clin Pharmacol 60, 623–628 (2004). https://doi.org/10.1007/s00228-004-0809-1
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DOI: https://doi.org/10.1007/s00228-004-0809-1