Abstract
The impact of the CYP2C19*17 allele on the pharmacokinetics of pantoprazole and omeprazole in previously studied children (n = 40) was explored. When pantoprazole area under the plasma concentration versus time curve (AUC) was examined as a function of CYP2C19 genotype, a significantly lower AUC was observed for subjects identified as CYP2C19*1/*1 and *1/*17. For pantoprazole, a statistically significant relationship was observed between CYP2C19 genotype and both dose-corrected AUC (p < 0.0001) and the apparent elimination rate constant (Kel; p = 0.0012); no significant genotype-phenotype relationships were observed for omeprazole.
Footnotes
This work was supported in part by the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant 1U01-HD31313-16] (Network of Pediatric Pharmacology Research Units) (infrastructure and salary support to J.S.L. and G.L.K.); and AstraZeneca, L.P. and Wyeth, who provided funding to support pharmacokinetic studies of omeprazole and pantoprazole, respectively.
Conflict of Interest: G.L.K. has served as a paid consultant for AstraZeneca, L.P. and Wyeth regarding the development of the pediatric programs for omeprazole and pantoprazole.
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.109.030601.
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The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.
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ABBREVIATIONS:
- PPI
- proton pump inhibitor
- SNP
- single nucleotide polymorphism
- AUC
- area under the plasma concentration versus time curve
- ANOVA
- analysis of variance
- Kel
- elimination rate constant.
- Received October 2, 2009.
- Accepted March 11, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Impact of the CYP2C19*17 Allele on the Pharmacokinetics of Omeprazole and Pantoprazole in Children: Evidence for a Differential Effect
