Short Communication Impact of the CYP2C19*17 Allele on the Pharmacokinetics of Omeprazole and Pantoprazole in Children: Evidence for a Differential Effect

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. CYP2C19*17 is characterized by 806C T (rs12248560) in the regulatory gene region and increases transcription levels. Subjects carrying CYP2C19*17 have higher CYP2C19 activity toward mephenytoin and omeprazole (Sim et al., 2006). There is limited information regarding the effect of CYP2C19*17 on the pharmacokinetics of CYP2C19 substrates in adults (Rudberg et al., 2008), and only a single study assessed the clinical outcome (Kurzawski et al., 2006). The goals of this exploratory study were as follows: 1) to characterize the effect of CYP2C19 genotype, especially the CYP2C19*17 allele, on the pharmacokinetics of two proton pump inhibitors (PPIs), omeprazole and pantoprazole, in a pediatric cohort and 2) to determine the frequency of CYP2C19*17 in population samples that represented different ethnic backgrounds. Materials and Methods Clinical Trials. The current investigation was enabled by a reassessment of data and samples available from previous pharmacokinetic studies of omeprazole (Kearns et al., 2003b) and pantoprazole (Kearns et al., 2008) conducted in pediatric populations for the purpose of product labeling. The Institutional Review Boards at participating institutions approved both investigations, and subjects were enrolled by parental permission and patient assent, as appropriate. The approvals contained provisions for data reanalysis and expanded genotype analysis of stored DNA specimens. Study designs, complete methods, and results were previously described in detail (Kearns et al., 2003b, 2008), and therefore only pertinent information is recapitulated in this brief