Correlation between R/S enantiomer ratio of lansoprazole and CYP2C19 activity after single oral and enteral administration |
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Authors: | Masatomo Miura Satoru Motoyama Yudai Hinai Takenori Niioka Makoto Hayakari Jun‐Ichi Ogawa Toshio Suzuki |
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Institution: | 1. Department of Pharmacy, Akita University Hospital, Akita, Japan;2. Department of Surgery, Akita University School of Medicine, Akita, Japan;3. Department of Pharmacy, Hirosaki University Hospital, Hirosaki, Japan |
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Abstract: | The purpose of this study was to investigate whether CYP2C19 activity can be estimated from plasma concentrations of lansoprazole enantiomers 4 h (C4h) after single administration by oral and enteral routes. Sixty‐nine subjects, 22 homozygous extensive metabolizers (homEMs), 32 heterozygous EMs (hetEMs), and 15 poor metabolizers (PMs), participated in the study. After a single oral or enteral dose of racemic lansoprazole (30 mg), plasma concentrations of lansoprazole enantiomers were measured 4 h postdose. The R/S ratio of lansoprazole at 4 h differed significantly among the three groups (P < 0.0001) regardless of the administration route. The R/S ratio of lansoprazole in CYP2C19 PMs ranged from 3.0 to 13.7, whereas in homEMs and hetEMs the ratio ranged from 8.6 to 90 and 2.1 to 122, respectively. The relationship between (S)‐lansoprazole concentration and R/S ratio of lansoprazole at C4h is given by the following formula: log10 R/S ratio] = 2.2 – 0.64 × log10 C4h of (S)‐lansoprazole] (r = 0.867, P < 0.0001). Thus, phenotyping CYP2C19 using the R/S enantiomer ratio of lansoprazole seems unlikely. However, to obtain a pharmacological effect similar to that in CYP2C19 PMs, we can presume that lansoprazole has a sufficient effect in the patient with an R/S enantiomer ratio at 4 h ≤ 13.70 and (S)‐lansoprazole concentration at 4 h ≥ 50 ng/ml. Chirality 2010. © 2009 Wiley‐Liss, Inc. |
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Keywords: | lansoprazole enantiomer CYP2C19 |
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