PT  - JOURNAL ARTICLE
AU  - Katarina Ilic
AU  - Roy L. Hawke
AU  - Ranjit K. Thirumaran
AU  - Erin G. Schuetz
AU  - J. Heyward Hull
AU  - Angela D.M. Kashuba
AU  - Paul W. Stewart
AU  - Celeste M. Lindley
AU  - Mei-Ling Chen
TI  - The Influence of Sex, Ethnicity, and <em>CYP2B6</em> Genotype on Bupropion Metabolism as an Index of Hepatic CYP2B6 Activity in Humans
AID  - 10.1124/dmd.112.048108
DP  - 2013 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 575--581
VI  - 41
IP  - 3
4099  - http://dmd.aspetjournals.org/content/41/3/575.short
4100  - http://dmd.aspetjournals.org/content/41/3/575.full
SO  - Drug Metab Dispos2013 Mar 01; 41
AB  - The effects of sex, ethnicity, and genetic polymorphism on hepatic CYP2B6 (cytochrome P450 2B6) expression and activity were previously demonstrated in vitro. Race/ethnic differences in CYP2B6 genotype and phenotype were observed only in women. To identify important covariates associated with interindividual variation in CYP2B6 activity in vivo, we evaluated these effects in healthy volunteers using bupropion (Wellbutrin SR GlaxoSmithKline, Research Triangle Park, NC) as a CYP2B6 probe substrate. A fixed 150-mg oral sustained-release dose of bupropion was administered to 100 healthy volunteers comprising four sex/ethnicity cohorts (n = 25 each): Caucasian men and Caucasian, African American, and Hispanic women. Blood samples were obtained at 0 and 6 hours postdose for the measurement of serum bupropion (BU) and hydroxybupropion (HB) concentrations. Whole blood was obtained at baseline for CYP2B6 genotyping. To characterize the relationship between CYP2B6 activity and ethnicity, sex, and genotype when accounting for serum BU concentrations (dose-adjusted log10-transformed), analysis of covariance model was fitted in which the dependent variable was CYP2B6 activity represented as the log10-transformed, metabolic ratio of HB to BU concentrations. Several CYP2B6 polymorphisms were associated with CYP2B6 activity. Evidence of dependence of CYP2B6 activity on ethnicity or genotype-by-ethnicity interactions was not detected in women. These results suggest that CYP2B6 genotype is the most important patient variable for predicting the level of CYP2B6 activity in women, when measured by the metabolism of bupropion. The bupropion metabolic ratio appears to detect known differences in CYP2B6 activity associated with genetic polymorphism, across different ethnic groups. Prospective studies will be needed to validate the use of bupropion as a probe substrate for clinical use.