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

نویسنده

  • Jacob Brown
چکیده

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

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

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 s...

متن کامل

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 sig...

متن کامل

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 sig...

متن کامل

Genotype and allele frequency of CYP2C19*17 in a healthy Iranian population

  Background: Cytochrome P450 2C19 (CYP2C19) is important in metabolism of wide range of drugs. CYP2C19*17 is a novel variant allele which increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (URM). Distribution of this variant allele has not been well studied worldwide. The aim of present study was to investigate allele and genotype frequencies of CYP2C19*17 ...

متن کامل

Population pharmacokinetics of omeprazole in a random Iranian population

Background: Omeprazole is metabolized predominantly by CYP2C19, a polymorphically expressed enzymes that show marked interindividual and interethnic variation. These variations cause a substantial differences that have been reported in the pharmacokinetics of omeprazole. The aim of the present study was to evaluate the pharmacokinetic parameters of omeprazole in a random Iranian population. Met...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2010