Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism.
BACKGROUND
Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19.


OBJECTIVE
To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C/9 genotypic status.


METHODS
Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n = 5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner.


RESULTS
The relative values for the area under the serum concentration-time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively.


CONCLUSIONS
The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen.
Ieiri
I
I
Department of Hospital Pharmacy, Faculty of Medicine, Tottori University, Japan. ieiri-ttr@umin.ac.jp
Kishimoto
Y
Y
Okochi
H
H
Momiyama
K
K
Morita
T
T
Kitano
M
M
Morisawa
T
T
Fukushima
Y
Y
Nakagawa
K
K
Hasegawa
J
J
Otsubo
K
K
Ishizaki
T
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000328:Adult; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D001562:Benzimidazoles / Q000737:chemistry / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005755:Gastrins / Q000097:blood*; D005838:Genotype; D006801:Humans; D064747:Lansoprazole; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D064750:Rabeprazole
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D005755:Gastrins; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064750:Rabeprazole; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000251:Adenosine Triphosphatases; D006180:Proton-Translocating ATPases; D009853:Omeprazole