Effects of clarithromycin on lansoprazole pharmacokinetics betweenCYP2C19genotypes

Abstract

AimsLansoprazole is a substrate of CYP2C19 and CYP3A. The aim of this study was to compare the inhibitory effects of clarithromycin, an inhibitor of CYP3A on the metabolism of lansoprazole betweenCYP2C19genotypes.MethodsA two‐way randomized double‐blind, placebo‐controlled crossover study was performed. Eighteen volunteers, of whom six were homozygous extensive metabolizers (EMs), six were heterozygous EMs and six were poor metabolizers (PMs) for CYP2C19, received two 6‐day courses of either clarithromycin 800 mg or placebo daily in a randomized fashion with a single oral dose of lansoprazole 60 mg on day 6 in all cases. Plasma concentrations of lansoprazole and its metabolites, 5‐hydroxylansoprazole and lansoprazole sulphone were monitored up to 24 h after dosing.ResultsDuring placebo administration, the mean AUC(0, ∞) of lansoprazole in homozygous EMs, heterozygous EMs and PMs were 4652 (95% CI, 2294, 7009) ng ml−1 h, 8299 (4784, 11814) ng ml−1 h and 25293 (17643, 32943) ng ml−1 h (P < 0.001), respectively. Clarithromycin treatment significantly increasedCmaxby 1.47‐fold, 1.71‐fold and 1.52‐fold and AUC(0, ∞) of lansoprazole by 1.55‐fold, 1.74‐fold, and 1.80‐fold in these genotype groups, respectively, whereas elimination half‐life was prolonged only in PMs. The clarithromycin‐mediated percent increase in pharmacokinetic parameters such asCmax, AUC(0, ∞) or elimination half‐life did not differ between the threeCYP2C19genotypes.ConclusionsThe present study indicates that there are significant drug interactions between lansoprazole and clarithromycin in allCYP2C19genotype groups probably through CYP3A inhibition. The bioavailability of lansoprazole might, to some extent, be increased through inhibition of P‐glycoprotein during clarithromycin treatment.