Effect of bupropion on CYP2B6 and CYP3A4 catalytic activity, immunoreactive protein and mRNA levels in primary human hepatocytes: comparison with rifampicin

• Published in: Journal of pharmacy and pharmacology Vol. 55; no. 9; p. 1229
• Main Authors: Hesse, Leah M, Sakai, Yumiko, Vishnuvardhan, Daesety, Li, Albert P, von Moltke, Lisa L, Greenblatt, David J
• Format: Journal Article
• Language: English
• Published: England 01.09.2003
• Subjects: Adult; Antidepressive Agents, Second-Generation - pharmacology; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Blotting, Western; Bupropion - pharmacology; Catalysis - drug effects; Cells, Cultured; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Female; Hepatocytes - cytology; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Immunohistochemistry; Middle Aged; Oxidoreductases, N-Demethylating - genetics; Oxidoreductases, N-Demethylating - metabolism; Rifampin - pharmacology; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 0022-3573
• DOI: 10.1211/0022357021657

Animals treated with multiple doses of bupropion have had increased bupropion clearance or increased liver weight, suggesting induction of drug-metabolizing activity. The possibility of cytochrome p450 (CYP) induction by bupropion (10 microM) was evaluated in-vitro by comparing catalytic activity, immunoreactive protein and CYP mRNA levels from human hepatocytes in primary culture versus cells treated with vehicle (0.5% methanol) and with rifampicin (rifampin) as a positive control. mRNA levels were analysed using a branched DNA luminescent assay. CYP2B6 activity, protein and mRNA levels were increased by 2.5, 1.5 and 2.1 fold, respectively, by 20 microM rifampicin. However, 10 microM bupropion minimally altered CYP2B6 (1.4, 1.1, 0.8 fold). Although CYP3A4 activity, protein, and mRNA levels were increased by 4.0, 2.3, and 14.0 fold, respectively, by 20 microM rifampicin, 10 microM bupropion minimally altered CYP3A4 (1.4, 1.0, 0.8 fold). Rifampicin (20 microM) increased CYP2E1 protein by 2.1 fold, while 10 microM bupropion minimally altered CYP2E1 protein (1.2 fold). Overall, results of this study suggest that multiple doses of bupropion are not likely to induce CYP2B6, 3A4 or 2E1 in-vivo in man.