Identification of poor and rapid metabolizers for the category of drugs metabolized by cytochrome P450 2B6 (CYP2B6) is important for understanding the differences in clinical responses of drugs metabolized by this enzyme. This study reports the prevalence of poor and rapid metabolizers in North Indian population residing in the National Capital Territory.The prevalence of poor and rapid metabolizers was determined in the target population for the category of drugs metabolized by CYP2B6 by measuring plasma bupropion, a drug metabolized by CYP2B6, and its metabolite. Bupropion (75 mg) was administered to 107 volunteers, and the drug (bupropion) and its metabolite (hydroxybupropion) were determined simultaneously by LCMS/MS in the plasma. CYP2B6 activity was measured as hydroxybupropion/bupropion ratio, and volunteers were categorized as rapid or poor metabolizers on the basis of cutoff value of log (hydroxybupropion/bupropion). Significant differences were observed between the mean metabolite/drug ratio of rapid metabolizers (Mean = 0.59) and poor metabolizers (Mean = 0.26) with p<0.0001. Results indicate that 20.56% individuals in the target population were poor metabolizers for the category of drugs metabolized by CYP2B6. Cutoff value defined in this study can be used as a tool for evaluating the status of CYP2B6 using bupropion as a probe drug. The baseline information would be clinically useful before administering the drugs metabolized by this isoform.

Identification of polymorphism of cytochrome P450 2C9 (CYP2C9) enzymes in different ethnic populations is important to understand the differences in clinical responses to drugs. This study determines the CYP2C9 genetic polymorphism in Indian National Capital Region and correlates the phenotype-genotype. Losartan (25 mg) was administered to 107 volunteers to assess CYP2C9 activity, and, on the basis of results, volunteers were categorized as rapid and poor metabolizers. Molecular typing of CYP2C9*1 (wild type), CYP2C9*2, and CYP2C9*3 (the most common variant) was carried out by single-base primer extension technology for 37 subjects, of which 9 were poor metabolizers, and 28 were rapid metabolizers. 14.28 % of the studied population was identified as poor metabolizer for the category of drugs metabolized by CYP2C9. Significant difference was observed between the mean ratio (drug/metabolite) of poor (11.38 ± 5.88) and rapid (1.18 ± 1.11) drug metabolizers. The study suggests that phenotyping of CYP2C9 is desirable before enrollment of subjects for clinical trials or for deciding drug dose regimen as 14.28 % of study population was found to be poor metabolizer for the category of drugs metabolized by CYP2C9. This study establishes phenotype-genotype correlation, and proposes to use genotyping or phenotyping to evaluate the status of drug metabolizing capacity of CYP2C9 as a primary screening procedure before enrolling subjects in clinical trials or in clinical practice.

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