Evaluation of the activity of CYP2C19 in Gujrati and Marwadi subjects living in Mumbai (Bombay)

All subjects received 20 mg of omeprazole, which was followed by blood collection at 3 hrs to estimate the metabolic ratio of omeprazole to 5-hydroxyomeprazole. The analysis was done by HPLC.It was seen that 10.36% of this population were poor metabolizers(PM) whereas 89.63% were extensive metabolizers(EM).A genotyping evaluation would better help in identifying population specific genotypes and thus help individualize drug therapy.The differences among individuals in the way they respond to medications [1] can be attributed to inherited differences in the metabolism and disposition of drugs, and genetic polymorphisms in the targets of drug therapy (e.g., receptors) [2-4] other than the conventional factors like individual's age and race, organ function, concomitant therapy, drug interactions, and concomitant illnesses [5]. CYP2C19, a member of the cytochrome P-450 enzyme superfamily(catalyzing phase I drug metabolism) [6] affects the metabolism of a number of clinically important drugs, such as proton pump inhibitors (omeprazole [7], lanzoprazole, rabeprazole), tricyclic antidepressants (imipramine, amitryptiline), phenytoin, propranolol and benzodiazepines (diazepam) [8]. Marked interethnic differences in the polymorphism frequency [6,9] have led to 21 variant alleles (CYP2C19*2 to CYP2C19*8) being documented; that predict poor metabolizers (PMs); of which the most commonly encountered ones contributing to a PM phenotype were CYP2C19*2 and CYP2C19*3 genotypes. The prevalence of PMs has been reported to be 2–5% in Caucasians [10,11], 4–8 % in Africans [12] and 11–23 % in Orientals [11].Polymorphisms can be determined by phenotyping and genotyping methodology. The phenotyping method employs the use of "Probe Drugs". These are drugs which are characteristically metabolized by a single enzyme system and hence can be used to classify individuals as extensive metabolizers (EMs) or poor metabolizers (PMs). The disadvantages in using older probe drugs like mephenytoin has