Abstract
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.
Highlights
Human cytochrome P450 2B6 (CYP2B6) is involved in the biotransformation of a variety of clinically important drugs such as the antiretroviral nevirapine (NVP) and efavirenz (EFV), which are used to treat AIDS and/or stop the spread of HIV infection (Erickson et al 1999; Ward et al 2003), antimalarial drug artemisinin (Simonsson et al 2003; Mehlotra et al 2006) and other drugs including cyclophosphamide, tamoxifen, diazepam, and bupropion (Lang et al 2001; Wang and Thompkins 2008)
Ethnic or racial interindividual CYP2B6 polymorphism in various populations has been reported in Caucasians (Lang et al 2001), Japanese (Hiratsuka et al 2002 and Hiratsuka et al 2004), African-American-Hispanic (Lamba et al 2003; Hesse et al 2004), Korean (Cho et al 2004), Mongolian (Davalkham et al 2009), Spain (Novoa et al 2005), and South Indians (Ramachandran et al 2009), but not in North Indian population, and, CYP2B6 was selected in this study
Aim of the study This study was aimed at to find out the prevalence of poor and rapid metabolizers for the category of drugs metabolized by CYP2B6 in the target population by measuring plasma bupropion, a drug metabolized by CYP2B6, and its metabolite
Summary
Human cytochrome P450 2B6 (CYP2B6) is involved in the biotransformation of a variety of clinically important drugs such as the antiretroviral nevirapine (NVP) and efavirenz (EFV), which are used to treat AIDS and/or stop the spread of HIV infection (Erickson et al 1999; Ward et al 2003), antimalarial drug artemisinin (Simonsson et al 2003; Mehlotra et al 2006) and other drugs including cyclophosphamide, tamoxifen, diazepam, and bupropion (Lang et al 2001; Wang and Thompkins 2008). CYP2B6 variant genotyping at baseline may allow clinicians to identify patients who are at risk of treatment failure or drug toxicity (Novoa et al 2005; Ramachandran et al 2009). Some of these variations are rare, but many are common, with allele frequencies between 10% and almost 50%, depending on the population (Klein et al 2005; Solus et al 2004). Ethnic or racial interindividual CYP2B6 polymorphism in various populations has been reported in Caucasians (Lang et al 2001), Japanese (Hiratsuka et al 2002 and Hiratsuka et al 2004), African-American-Hispanic (Lamba et al 2003; Hesse et al 2004), Korean (Cho et al 2004), Mongolian (Davalkham et al 2009), Spain (Novoa et al 2005), and South Indians (Ramachandran et al 2009), but not in North Indian population, and, CYP2B6 was selected in this study
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