Influence of CYP2C19 and ABCB1 polymorphisms on plasma concentrations of lansoprazole enantiomers after enteral administration.
An intraoral annihilation enteric-coated preparation of lansoprazole is often administered via intestinal fistula. The purpose of this study was to determine the plasma concentrations of lansoprazole enantiomers after enteral administration in subjects with cytochrome P4502C19 (CYP2C19) and ABCB1 C3435T genotypes. Fifty-one patients who underwent a curative oesophagectomy for oesophageal cancer were enrolled in this study. After a single enteral dose of racemic lansoprazole (30 mg), plasma concentrations of lansoprazole enantiomers were measured 4 h post-dose (C(4h)). There were significant differences in the C(4h) of (R)- and (S)-lansoprazole and the R/S-enantiomer ratio for three CYP2C19 genotype groups (*1/*1, *1/*2 ± *1/*3, and *2/*2 ± *2/*3 ± *3/*3 (poor metabolizers (PMs)), but not the ABCB1 C3435T genotypes. In a stepwise forward selection multiple regression analysis, the C(4h) of (R)- and (S)-lansoprazole were associated with CYP2C19 PMs (p = 0.0005 and < 0.0001 respectively) and age (p = 0.0040 and 0.0121 respectively), while the R/S-enantiomer ratio was associated with CYP2C19*1/*1 (p = 0.0191) and CYP2C19 PMs (p = 0.0426). Direct administration to the jejunum is unaffected by residence time in the stomach and the gastric emptying rate. With enteral administration, CYP2C19 phenotyping of patients using the lansoprazole R/S enantiomer index at C(4h) could be possible.
Miura
Masatomo
M
Department of Pharmacy, Akita University Hospital, Akita, Japan. m-miura@hos.akita-u.ac.jp
Motoyama
Satoru
S
Hinai
Yudai
Y
Niioka
Takenori
T
Endo
Masahiro
M
Hayakari
Makoto
M
Ogawa
Jun-ichi
J
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry* / Q000627:therapeutic use; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D004750:Enteral Nutrition; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D004938:Esophageal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D013237:Stereoisomerism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004791:Enzyme Inhibitors; D064747:Lansoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19