Effect of MDR1 C3435T polymorphism on lansoprazole in healthy Japanese subjects.
OBJECTIVE
The effect of multidrug resistance transporter gene 1 (MDR1) on the bioavailability and kinetics of several substrates has not yet been fully elucidated. We evaluated the influence of MDR1 C3435T polymorphism on the pharmacokinetics and pharmacodynamics of lansoprazole in Japanese subjects.


METHODS
Fifteen healthy volunteers with the rapid extensive metabolizer genotype of CYP2C19 were classified into three MDR1 C3435T genotype groups: C/C (n = 5), C/T (n = 5), and T/T (n = 5). Lansoprazole 30 mg was administered orally for 15 days. The intragastric pH and plasma lansoprazole levels were determined on days 1 and 15.


RESULTS
On day 1, the mean C(max) of lansoprazole in the T/T group was significantly higher than that in the C/C or C/T groups (T/T 1,248, C/C 618, C/T 607 ng/ml; P = 0.038). On day 15, similar MDR1 genotype-dependent differences were observed in the C(max) of lansoprazole, although smaller than the differences observed on day 1. In contrast, the intragastric pH attained after lansoprazole administration did not differ among MDR1 genotype groups on either day 1 or day 15.


CONCLUSIONS
Although the sample size was small, our study demonstrated that the MDR1 C3435T polymorphism influenced the pharmacokinetics, but not the pharmacodynamics (i.e., intragastric pH), of lansoprazole in rapid metabolizers of CYP2C19.
Kodaira
Chise
C
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Sugimoto
Mitsushige
M
Nishino
Masafumi
M
Yamade
Mihoko
M
Shirai
Naohito
N
Uchida
Shinya
S
Ikuma
Mutsuhiro
M
Yamada
Shizuo
S
Watanabe
Hiroshi
H
Hishida
Akira
A
Furuta
Takahisa
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000493:pharmacokinetics*; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D064747:Lansoprazole; D008297:Male; D011110:Polymorphism, Genetic; D012015:Reference Standards
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000897:Anti-Ulcer Agents; D064747:Lansoprazole