Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2005 Mar;59(3):302-9.
doi: 10.1111/j.1365-2125.2004.02329.x.

Effects of clarithromycin on lansoprazole pharmacokinetics between CYP2C19 genotypes

Masato Saito  1 , Norio Yasui-Furukori, Tsukasa Uno, Takenori Takahata, Kazunobu Sugawara, Akihiro Munakata, Tomonori Tateishi
Affiliations
Clinical Trial

Effects of clarithromycin on lansoprazole pharmacokinetics between CYP2C19 genotypes

Masato Saito et al. Br J Clin Pharmacol. 2005 Mar.

Abstract

Aims: Lansoprazole 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 between CYP2C19 genotypes.

Methods: A 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.

Results: During placebo administration, the mean AUC0, infinity 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 increased Cmax by 1.47-fold, 1.71-fold and 1.52-fold and AUC0, infinity 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 as Cmax, AUC0, infinity or elimination half-life did not differ between the three CYP2C19 genotypes.

Conclusions: The present study indicates that there are significant drug interactions between lansoprazole and clarithromycin in all CYP2C19 genotype groups probably through CYP3A inhibition. The bioavailability of lansoprazole might, to some extent, be increased through inhibition of P-glycoprotein during clarithromycin treatment.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Mean plasma concentration-time curves of lansoprazole during placebo and clarithromycin treatment in homozygous extensive metabolizers (EMs) (n = 6), heterozygous EMs (n = 6), and poor metabolizers (PMs) (n = 6) for CYP2C19. Data are shown as mean and bars are SDs. Open circles and closed squares indicate data during placebo and clarithromycin treatments, respectively.
Figure 2
Figure 2
Effects of CYP2C19 genotypes on the mean clarithromycin-mediated percent increase in peak concentration (Cmax), the area under the concentration-time curve from zero to infinity (AUC(0, ∞)) and elimination half-life of lansoprazole. Error bars indicate SD.
Figure 3
Figure 3
Effects of CYP2C19 genotypes on the mean clarithromycin-mediated percent change in the area under concentration-time curve from zero to infinity (AUC(0, ∞)) ratio of 5-hydroxylansoprazole to lansoprazole and the AUC(0, ∞) ratio of lansoprazole sulphone to lansoprazole, respectively. Error bars indicate SD
See this image and copyright information in PMC

Comment in

References

    1. Nagaya H, Satoh H, Maki Y. Possible mechanism for the inhibition of acid formation by the proton pump inhibitor AG-1749 in isolated canine parietal cells. J Pharmacol Exp Ther. 1990;252:1289–95. - PubMed
    1. Spencer CM, Lansoprazole Faulds D. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy in acid-related disorders. Drugs. 1994;48:404–30. - PubMed
    1. Landes BD, Miscoria G, Flouvat B. Determination of lansoprazole and its metabolites in plasma by high-performance liquid chromatography using a loop column. J Chromatogr. 1992;577:117–22. - PubMed
    1. Pearce RE, Rodrigues AD, Goldstein JA, Parkinson A. Identification of the human P450 enzymes involved in lansoprazole metabolism. J Pharmacol Exp Ther. 1996;277:805–16. - PubMed
    1. Kim KA, Kim MJ, Park JY, Shon JH, Yoon YR, Lee SS, et al. Stereoselective metabolism of lansoprazole by human liver cytochrome P450 enzymes. Drug Metab Dispos. 2003;31:1227–34. - PubMed

Publication types

MeSH terms