Alcohol is consumed worldwide in tremendous amounts. Depending on exposure duration, alcohol induces or inhibits drug metabolism. Human liver microsomes from donors reported to have consumed at least 14 alcoholic beverages per week have high CYP2B6 activity (bupropion hydroxylation) per milligram of microsomal protein in vitro. Furthermore, high CYP2B6 activity correlates significantly with the absence of a CYP2B6*6B allele.
The aims of this research are to test the hypotheses that 1) alcohol induces bupropion hydroxylation (CYP2B6 probe), and 2) the presence of at least one CYP2B6*6B allele restricts this inductive effect, supporting in vitro results. The pharmacokinetics of bupropion and hydroxybupropion will be assessed in a three-group clinical study involving healthy volunteers who typically drink or abstain from alcohol. Pharmacokinetics will be compared in drinkers with at least one CYP2B6*6B allele versus drinkers with no CYP2B6*6B allele. Results will provide clinical data on the inducibility of CYP2B6 by alcohol. Results may indicate that genotyping patients is advantageous before prescribing a CYP2B6 substrate to perhaps avoid adverse events such as seizures (bupropion) or inefficient HIV therapy (efavirenz).

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AA015647-01A1
Application #
7058151
Study Section
Special Emphasis Panel (ZAA1-HH (40))
Program Officer
Guo, Qingbin
Project Start
2005-09-20
Project End
2008-09-19
Budget Start
2005-09-20
Budget End
2006-09-19
Support Year
1
Fiscal Year
2005
Total Cost
$48,296
Indirect Cost
Name
Tufts University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
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Kaivosaari, Sanna; Toivonen, Paivi; Hesse, Leah M et al. (2007) Nicotine glucuronidation and the human UDP-glucuronosyltransferase UGT2B10. Mol Pharmacol 72:761-8