Cho, Doo-YeounShen, Joan H.Q.Lemler, Suzanne M.Skaar, Todd C.Li, LangBlievernicht, JuliaZanger, Ulrich M.Kim, Kwon-BokShin, Jae-GookFlockhart, David A.Desta, Zeruesenay2017-05-242017-05-242016-04Cho, D.-Y., Shen, J. H. Q., Lemler, S. M., Skaar, T. C., Li, L., Blievernicht, J., … Desta, Z. (2016). Rifampin enhances cytochrome P450 (CYP) 2B6-mediated efavirenz 8-hydroxylation in healthy volunteers. Drug Metabolism and Pharmacokinetics, 31(2), 107–116. http://doi.org/10.1016/j.dmpk.2015.07.002https://hdl.handle.net/1805/12720The effect of rifampin on the in vivo metabolism of the antiretroviral drug efavirenz was evaluated in healthy volunteers. In a cross-over placebo control trial, healthy subjects (n = 20) were administered a single 600 mg oral dose of efavirenz after pretreatment with placebo or rifampin (600 mg/day for 10 days). Plasma and urine concentrations of efavirenz, 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz were measured by LC-MS/MS. Compared to placebo treatment, rifampin increased the oral clearance (by ∼2.5-fold) and decreased maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0-∞) of efavirenz (by ∼1.6- and ∼2.5-fold respectively) (p < 0.001). Rifampin treatment substantially increased the Cmax and AUC0-12h of 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz, metabolic ratio (AUC0-72h of metabolites to AUC0-72h efavirenz) and the amount of metabolites excreted in urine (Ae0-12hr) (all, p < 0.01). Female subjects had longer elimination half-life (1.6-2.2-fold) and larger weight-adjusted distribution volume (1.6-1.9-fold) of efavirenz than male subjects (p < 0.05) in placebo and rifampin treated groups respectively. In conclusion, rifampin enhances CYP2B6-mediated efavirenz 8-hydroxylation in vivo. The metabolism of a single oral dose of efavirenz may be a suitable in vivo marker of CYP2B6 activity to evaluate induction drug interactions involving this enzyme.en-USPublisher Policy8-HydroxylationCYP2B6EfavirenzInductionIn vivo probeRifampinArticle