Nevirapine induces both CYP3A4 and CYP2B6 metabolic pathways

Abstract

Clinical Pharmacology & Therapeutics (1999) 65, 137–137; doi:

Comparative Study of the Effects of Antituberculosis Drugs and Antiretroviral Drugs on Cytochrome P450 3A4 and P-Glycoprotein

“…Likewise, all the intended macrolides exhibited inhibitory effects on CYP3A4 at several levels (Table 2). Compared to previous studies using human liver microsomes (HLMs), the inhibitory concentration for INH presented here was evidently low (IC 50 , 0.9 M) ( Table 2) (23, 24). Both PZA and EMB exerted no effects on CYP3A4 at any given concentration (see Table S1 in the supplemental material).…”

“…Hence, we inferred that the DDIs between NVP and CYP3A4 modulators, such as azoles, HIV protease inhibitors, and oral contraceptives, would depend on CYP2B6 induction by NVP, because these CYP3A4 modulators have been proven to be substrates for CYP2B6 (29,48,49). However, the increased metabolism of ERY mediated by NVP cannot be explained with this hypothesis, because macrolides have no bearing on CYP2B6 activities (data not shown) (50). In the light of previous studies, NVP might exhibit both inductive and inhibitory effects on CYP3A4 activity on a case-by-case basis (47).…”

“…This experiment was performed to measure the inhibitory effects of each agent on the metabolism of a nonfluorescent CYP3A4 substrate, 7-benzyloxy-trifluoromethylcoumarin (BFC), to a fluorescent metabolite, 7-hydroxyl-trifluoromethylcoumarin (HFC), according to the manufacturer's instructions, except for the plate-reading conditions, which were set at an excitation of 405 nm and an emission of 535 nm. The 50% inhibitory concentration (IC 50 ) values of each drug were calculated by linear interpolation. The standard curve of HFC was prepared over the range of 2,000 to 0.9 pmol.…”

Population pharmacokinetics of nevirapine in combination with rifampicin-based short course chemotherapy in HIV- and tuberculosis-infected South African patients

“…Ethambutol is included in the continuation phase in those patients who have had a previous episode of TB. Nevirapine is both metabolized by and induces cytochrome P450 (CYP) isoenzymes 3A4 and 2B6 [3]. The plasma concentrations of nevirapine initially decrease after the start of therapy due to auto-induction, reaching a steady state during the second week of treatment [3,4].…”

“…Nevirapine is both metabolized by and induces cytochrome P450 (CYP) isoenzymes 3A4 and 2B6 [3]. The plasma concentrations of nevirapine initially decrease after the start of therapy due to auto-induction, reaching a steady state during the second week of treatment [3,4]. Rifampicin is a potent inducer of CYP3A4 and increases the expression of CYP2B6 [5,6].…”