Anacetrapib
Anacetrapib neither inhibits nor induces CYP3A, but ketoconazole raises its own exposure more than fourfold (J Clin Pharmacol 2009)
Original title: Assessment of the CYP3A-mediated drug interaction potential of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy volunteers
Two partially blinded, randomized, fixed-sequence studies used midazolam, a sensitive CYP3A probe substrate, to test whether anacetrapib affects CYP3A activity, and ketoconazole, a potent CYP3A inhibitor, to test how strong CYP3A inhibition affects the pharmacokinetics of anacetrapib itself. All treatments were generally well tolerated. Geometric mean ratios (90% CI) for midazolam with anacetrapib versus midazolam alone were 1.04 (0.94, 1.14) for AUC0-infinity and 1.15 (0.97, 1.37) for Cmax, showing no meaningful effect. In contrast, ketoconazole substantially raised anacetrapib exposure, with geometric mean ratios of 4.58 (3.68, 5.71) for AUC0-infinity and 2.37 (2.02, 2.78) for Cmax, demonstrating anacetrapib neither inhibits nor induces CYP3A activity but is itself a moderately sensitive CYP3A substrate whose exposure rises substantially with strong CYP3A inhibitors.
Original abstract
In this study, midazolam was used as a probe-sensitive CYP3A substrate to investigate the effect of anacetrapib on CYP3A activity, and ketoconazole was used as a probe-inhibitor to investigate the effect of potent CYP3A inhibition on the pharmacokinetics of anacetrapib, a novel cholesteryl ester transfer protein inhibitor in development for the treatment of dyslipidemia. Two partially blinded, randomized, 2-period, fixed-sequence studies were performed. Safety, tolerability, and midazolam and anacetrapib plasma concentrations were assessed. All treatments were generally well tolerated. The geometric mean ratios (90% confidence interval) of midazolam with anacetrapib/midazolam alone for AUC0-infinity and Cmax were 1.04 (0.94, 1.14) and 1.15 (0.97, 1.37), respectively. Exposure to anacetrapib was increased by ketoconazole--specifically, the geometric mean ratios (90% confidence interval) of anacetrapib with ketoconazole/anacetrapib alone for AUC0-infinity and Cmax were 4.58 (3.68, 5.71) and 2.37 (2.02, 2.78), respectively. The study showed that anacetrapib does not inhibit or induce CYP3A activity. Furthermore, anacetrapib appears to be a moderately sensitive substrate of CYP3A.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.