title: Correlation between R/S enantiomer ratio of lansoprazole and CYP2C19 activity after single oral and enteral administration.
abstract: The purpose of this study was to investigate whether CYP2C19 activity can be estimated from plasma concentrations of lansoprazole enantiomers 4 h (C(4h)) 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 C(4h) is given by the following formula: log(10) [R/S ratio] = 2.2 - 0.64 x log(10) [C(4h) 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 < or = 13.70 and (S)-lansoprazole concentration at 4 h > or = 50 ng/ml.
authors.affiliation: Department of Pharmacy, Akita University Hospital, Akita, Japan. m-miura@hos.akita-u.ac.jp
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.forename: Satoru
authors.initials: S
authors.lastname: Motoyama
authors.forename: Yudai
authors.initials: Y
authors.lastname: Hinai
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayakari
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Ogawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry*; D000284:Administration, Oral; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D065731:Cytochrome P-450 CYP2C19; D057075:Enzyme Assays / Q000379:methods*; D005260:Female; D005838:Genotype; D006801:Humans; D064747:Lansoprazole; D008297:Male; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D064747:Lansoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19