Abstract
Since antiretroviral drugs are known to inhibit many cytochrome P450 isoforms, the inhibition of CYP2B6 by non-nucleoside reverse transcriptase inhibitors and viral protease inhibitors was studied in vitro in human liver microsomes using bupropion hydroxylation as the CYP2B6 index reaction. Mean IC50 values (μM) for inhibition of bupropion hydroxylation were: nelfinavir (2.5), ritonavir (2.2), and efavirenz (5.5). The reaction was only weakly inhibited by indinavir, saquinavir, amprenavir, delavirdine, and nevirapine. The inhibition of bupropion hydroxylation in vitro by nelfinavir, ritonavir, and efavirenz indicates inhibitory potency versus CYP2B6 and suggests the potential for clinical drug interactions.
Footnotes
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Send reprint requests to: Dr. David J. Greenblatt, Dept. of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA. E-mail:DJ.Greenblatt{at}tufts.edu
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This work was supported in part by Grants MH34223, MH01237, MH58435, DA05258, DA13209, and RR00054 from the Department of Health and Human Services.
- Abbreviation used is::
- CYP
- cytochrome P450
- Received September 18, 2000.
- Accepted November 6, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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