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 20 mg 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 ng ml−1, respectively) and 6.9-fold (4787 ± 3454 vs. 451 ± 354 ng h ml−1, respectively) greater, and its elimination half-life was 2.1-fold (2.3 ± 1.0 vs. 1.2 ± 0.6 h, 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 ± 0.9 h, respectively; P < 0.05), there was no difference in Cmax between the (R)- and (S)-enantiomer (186 ± 40 vs. 200 ± 92 ng ml−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.