Anacetrapib
Chronic rifampin dosing slashes anacetrapib exposure by 65% through CYP3A induction, while a single dose barely moves it (J Clin Pharmacol 2013)
Original title: Effects of Rifampin, a potent inducer of drug-metabolizing enzymes and an inhibitor of OATP1B1/3 transport, on the single dose pharmacokinetics of anacetrapib
This open-label, fixed-sequence, three-period study tested whether anacetrapib is a victim of OATP1B1/3 transporter inhibition or CYP3A induction, using acute and chronic rifampin dosing as a probe. Sixteen healthy subjects received anacetrapib 100 mg alone, then with a single 600 mg dose of rifampin, then with 600 mg rifampin daily for 20 days. Single-dose rifampin, which inhibits OATP1B1/3, produced modest increases in anacetrapib AUC0-infinity and Cmax (geometric mean ratios 1.25, 90% CI 1.04-1.51, and 1.43, 90% CI 1.13-1.82). Multiple-dose rifampin, which strongly induces CYP3A, instead sharply reduced anacetrapib AUC0-infinity and Cmax (geometric mean ratios 0.35, 90% CI 0.29-0.42, and 0.26, 90% CI 0.21-0.32), cutting mean systemic exposure by 65%. Anacetrapib was well tolerated throughout, and the results indicate CYP3A induction, not OATP1B1/3 inhibition, is the clinically important interaction pathway for anacetrapib.
Original abstract
Anacetrapib is a novel cholesteryl ester transfer protein (CETP) inhibitor in development for treatment of dyslipidemia. This open-label, fixed-sequence, 3-period study was intended to evaluate the potential of anacetrapib to be a victim of OATP1B1/3 inhibition and strong CYP3A induction using acute and chronic dosing of rifampin, respectively, as a probe. In this study, 16 healthy subjects received 100 mg anacetrapib administered without rifampin (Day 1, Period 1), with single-dose (SD) 600 mg rifampin (Day 1, Period 2), and with multiple-dose (MD) 600 mg rifampin for 20 days (Day 14, Period 3). Log-transformed anacetrapib AUC0-∞ and Cmax were analyzed by a linear mixed effects model. The GMRs and 90% CIs for anacetrapib AUC0-∞ and Cmax were 1.25 (1.04, 1.51) and 1.43 (1.13, 1.82) for SD rifampin (Period 2/Period 1) and 0.35 (0.29, 0.42) and 0.26 (0.21, 0.32) for MD rifampin (Period 3/Period 1), respectively. Anacetrapib was generally well tolerated in both the absence/presence of SD and MD rifampin. In conclusion, treatment with SD rifampin, which inhibits the OATP1B1/3 transporter system, did not substantially influence the SD pharmacokinetics of anacetrapib, while chronic (20 days) administration of rifampin, which strongly induces CYP3A isozymes, reduced mean systemic exposure to SD anacetrapib by 65%.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.