Author's reply: Hydroxylation of lansoprazole in poor metabolizers of CYP2C19
Abstract
We appreciated the comments from Dr Furuta and colleagues regarding the hydroxylation of lansoprazole in poor metabolizers for CYP2C19. Dr Furuta and colleagues noted a discrepancy in the hydroxylation between omeprazole and lansoprazole, i.e. the AUC of hydroxyomeprazole decreased during clarithromycin co-administration in poor metabolizers (PMs) for CYP2C19 [1] while that of hydroxylansoprazole increased during clarithromycin co-administration in PMs for CYP2C19 [2]. As Dr Furuta and colleagues pointed out, it would be expected that the AUC of hydroxylansoprazole would decrease during co-administration of clarithromycin, a CYP3A4 inhibitor, in PMs for CYP2C19 if hydroxylation is mediated by CYP3A4 [3, 4]. Therefore the findings of increased hydroxylansoprazole might imply an alternative pathway of elimination. A recent in vitro study demonstrated that predicted CLint (µl min−1 nmol−1 of P450) of hydroxylation of R- and S-lansoprazole in human liver microsomes were 0.1 and 0.75 for CYP2C9, 1.32 and 1.65 for CYP2C19 and 0.46 and 0.35 for CYP3A4, respectively [5]. These results suggest that CYP2C9 is also an enzyme involved in the hydroxylation of lansoprazole in PMs for CYP2C19. In our study, the CYP2C9 genotype of the subjects were all *1/*1, which suggests normal activity of CYP2C9. In addition, the hydroxylation index (AUC ratio of hydroxylansoprazole : lansoprazole) did not differ [2]. Because sulfoxidation of lansoprazole is inhibited by clarithromycin through CYP3A4,…
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