Genetic Polymorphism of CYP2C19: An Assessment of In-vivo Activity

Abstract

The present study aimed as a first attempt on the North Indian population to establish the CYP2C19 phenotype frequencies among the population of Uttarakhand. A total of 20 physically healthy and unrelated human subjects of either sex (both male and female), with age range from 18-30 yrs, body weight ≥ 40 kg, participated in this study. After an overnight fast, each subject received a single dose of 20 mg omeprazole capsule orally. Blood samples (5ml) were collected just before (at 0 hr) and 3 hr after the drug administration. Plasma was separated after centrifugation and stored at -20ºC until analysis. The plasma concentrations of omeprazole and its metabolite, 5- hydroxyomeprazole, were determined by using High performance liquid chromatography (HPLC) method of analysis with some modifications. The metabolites were separated using a mixture of acetonitrile: 0.05 M phosphate buffer (20:80, ph 8.5) at flow rate of 1.5 ml/min. Metabolites were detected by their absorbance at 250 nm. Amounts were calculated from standard curves of omeprazole and its metabolite constructed in the concentration range of 10–1000 ng/ml. Out of 20 subjects, 17 (85%) were EMs and 03 (15%) were PMs. The prevalence of PMs in study population of Uttarakhand was found to be 15% by phenotyping, which is slightly greater than frequencies of South Indians (14%), Gujratis and Marwadis (10.32%), Southeast Asians like Thai (9.2%), Burmese (11%) and Karen (8.4%), Koreans (12.6%) and some other North Indians (10-12%). On the other hand, this PM frequency of 15% is found to be lower than the frequency found in Mexicans (31%), Japanese (27-35%). Our study population possesses 15% PMs, which is essential to evaluate the phenotypegenotypes correlation in this population after the genotyping data is available. It is now further suggested that future studies on genetic polymorphism on subjects of Uttarakhand be carried out on large study population for better interpretation and may involve the correlation of phenotype-genotype data along with observations that relate them to the findings such as adverse drug reaction monitoring, drug therapy decisions like cost and duration of therapy.