Pharmacokinetic Interaction Among Ezetimibe, Rosuvastatin, and Telmisartan

Abstract

To evaluate the pharmacokinetic interactions among rosuvastatin, ezetimibe, and telmisartan, a randomized, open-label, 3-period, 6-sequence crossover study was conducted in healthy subjects. Subjects received one of the following treatments once daily for 7 days in each period with a 1-week washout: a fixed-dose combination of ezetimibe/rosuvastatin 10/20 mg, telmisartan 80 mg, combination therapy of ezetimibe/rosuvastatin 10/20 mg, or telmisartan 80 mg. Blood samples were collected up to 24 hours postdose at steady state. Geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) of the combination therapy to monotherapy for the maximum plasma concentration (C_max,ss ), and the area under the time-concentration curve within a dosing interval at steady state (AUC_tau,ss ) were estimated. Among the 36 randomized subjects, 31 subjects completed the study. The GMRs and 90%CIs of C_max,ss and AUC_tau,ss of total ezetimibe were not significantly altered. The C_max,ss of free ezetimibe was increased (GMR, 1.85; 90%CI, 1.56-2.19) but not for the AUC_tau,ss (GMR, 1.16; 90%CI, 1.06-1.26). Similarly, the C_max,ss of rosuvastatin was increased (GMR, 2.13; 90%CI, 1.88-2.43) without a change in the AUC_tau,ss (GMR, 1.09; 90%CI, 1.03-1.15). The C_max,ss (GMR, 1.16; 90%CI, 1.01-1.32) and AUC_tau,ss (GMR, 1.26; 90%CI, 1.17-1.37) of telmisartan were slightly increased. Considering the therapeutic range of the components, the interaction would have limited clinical impact.

Trial registration: ClinicalTrials.gov NCT03586037.

Keywords: drug-drug interactions; dyslipidemia; ezetimibe; hypertension; rosuvastatin; telmisartan.