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Background  Polymorphism of  CYP2C19  gene is one of the important factors in pharmacokinetics of CYP2C19 substrates. Omeprazole is a proton pump inhibitor which is mainly metabolized by cytochrome P450 2C19 ( CYP2C19 ). The aim of present study was to assess omeprazole hydroxylation index as a measure of CYP2C19 activity considering new variant allele ( CYP2C19*17 ) in Iranian population and also to see if this activity is sex dependent.    Methods  One hundred and eighty healthy unrelated Iranian individuals attended in this study. Blood samples for genotyping and phenotyping were collected 3 hours after administration of 20 mg omeprazole orally. Genotyping of  2C19  variant alleles  *2 ,  *3  and  *17  was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and semi-nested PCR methods. Plasma concentrations of omeprazole and hydroxyomeprazole were determined by high performance liquid chromatography (HPLC) technique and hydxroxylation index (HI) (omeprazole/ hydroxyomeprazole) was calculated.    Results  The  CYP2C19*17  was the most common variant allele in the studied population (21.6%). Genotype frequencies of  CYP2C19*17*17 ,  *1*17 , and  *2*17  were 5.5%, 28.8% and 3.3% respectively. The lowest and the highest median omeprazole HI was observed in  *17*17  and  *2*2  genotypes respectively (0.36 vs. 13.09). The median HI of omeprazole in subjects homozygous for  CYP2C19*1  was 2.16-fold higher than individuals homozygous for  CYP2C19*17  (P < 0.001) and the median HI of  CYP2C19*1*17  genotype was 1.98-fold higher than  CYP2C19 *17*17  subjects (P < 0.001). However, subjects with  CYP2C19*2*17  (median HI: 1.74) and  CYP2C19*1*2  (median HI: 1.98) genotypes and also  CYP2C19*1*17  (median HI: 0.71) and  CYP2C19*1*1  (mean HI: 0.78) did not show any significantly different enzyme activity. In addition, no statistically significant difference was found between women and men in distribution of  CYP2C19  genotypes. Furthermore, the hydroxylation index of Omeprazole was not different between women and men in the studied population.    Conclusion  Our data point out the importance of  CYP2C19*2  and  CYP2C19*17  variant alleles in metabolism of omeprazole and therefore CYP2C19 activity. Regarding the high frequency of  CYP2C19*17  in Iranian population, the importance of this new variant allele in metabolism of CYP2C19 substrates shall be considered.

Hydroxylation index of omeprazole in relation to CYP2C19 polymorphism and sex in a healthy Iranian population