Comparison of enantioselective disposition of rabeprazole versus lansoprazole in renal-transplant recipients who are CYP2C19 extensive metabolizers.
The purpose of this study was to investigate the comparative pharmacokinetics of rabeprazole and lansoprazole enantiomers in renal-transplant recipients on tacrolimus who were CYP2C19 extensive metabolizers. Sixteen Japanese patients were randomly assigned after renal transplantation to receive repeated doses of one of the following two regimens for 28 days; tacrolimus, mycophenolate mofetil and prednisolone together with either 20mg of racemic rabeprazole (n=8) or 30 mg of racemic lansoprazole (n=8). The mean Cmax and AUC0-24 of (R)-lansoprazole compared to (S)-lansoprazole in renal transplant recipients were 12-fold (954+/-522 vs. 167+/-137 ngml(-1), respectively) and 6.9-fold (4787+/-3454 vs. 451+/-354 nghml(-1), respectively) greater, and its elimination half-life was 2.1-fold (2.3+/-1.0 vs. 1.2+/-0.6h, respectively) longer. In contrast, although the elimination half-life of (R)-rabeprazole was significantly longer than that of the (S)-enantiomer (2.1+/-0.5 vs. 1.3+/-0.9h, respectively; P<0.05), there was no difference in Cmax between the (R)- and (S)-enantiomer (186+/-40 vs. 200+/-92 ngml(-1), respectively). In conclusion, in renal-transplant recipients who are CYP2C19 extensive metabolizers, there is less stereoselective difference in the pharmacokinetic disposition between the (R)- and (S)-enantiomers of rabeprazole than those of lansoprazole.
Miura
M
M
Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan.
Kagaya
H
H
Tada
H
H
Sagae
Y
Y
Satoh
S
S
Habuchi
T
T
Suzuki
T
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001562:Benzimidazoles / Q000493:pharmacokinetics*; D065731:Cytochrome P-450 CYP2C19; D064748:Dexlansoprazole; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D064747:Lansoprazole; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D064750:Rabeprazole; D013237:Stereoisomerism; D013379:Substrate Specificity; D016559:Tacrolimus / Q000627:therapeutic use
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D007166:Immunosuppressive Agents; D064747:Lansoprazole; D064750:Rabeprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D064748:Dexlansoprazole; D016559:Tacrolimus