Hydroxylation of lansoprazole in poor metabolizers of CYP2C19

摘要

We read the recent paper by Saito et al. with interest. The theme of their paper was quite similar to the one we published 6 years ago . However, there was one curious point in the results. Individuals with the poor metabolizer (PM) genotype of CYP2C19 lack the CYP2C19 enzyme therefore hydroxylation of lansoprazole is assumed to be mediated by CYP3A4, as was explained briefly in the introduction section. Accordingly, hydroxylansoprazole concentrations should be decreased by clarithromycin in PMs because clarithro-mycin strongly inhibits the activity of CYP3A4, as we observed in our previous paper . However, in the present paper, hydroxylansoprazole concentrations were increased by clarithromycin, just as observed in extensive metabolizers (EMs). The results of the present study by Saito etal. indicated that the hydroxylation of lansoprazole in PMs was not mediated by CYP3A4, but by another enzyme which was not influenced by clarithromycin. We would like to know the candidate enzyme or an explanation for the discrepant results. #