An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers

Abstract

Background: Rosuvastatin and fenofibrate are lipid-regulating agents with different modes of action. Patients with dyslipidemia who have not achieved treatment targets with monotherapy may benefit from the combination of these agents.Objective: The effect of coadministration of rosuvastatin and fenofibrate on the steady-state pharmacokinetics of rosuvastatin and fenofibric acid (the active metabolite of fenofibrate) was assessed in healthy volunteers.Methods: This was an open-label, randomized, 3-way crossover trial consisting of three 7-day treatment periods. Healthy male volunteers received one of the following treatment regimens in each period: rosuvastatin 10 mg orally once daily; fenofibrate 67 mg orally TID; and rosuvastatin + fenofibrate dosed as above. The steady-state pharmacokinetics of rosuvastatin and fenofibric acid, both as substrate and as interacting drug, were investigated on day 7 of dosing. Treatment effects were assessed by construction of 90% CIs around the ratios of the geometric least-square means for rosuvastatin + fenofibrate/rosuvastatin and rosuvastatin + fenofibrate/fenofibrate for the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (derived from analysis of variance of log-transformed parameters).Results: Fourteen healthy male volunteers participated in the study. When rosuvastatin was coadministered with fenofibrate, there were minor increases in the AUC from 0 to 24 hours and maximum concentration (Cmax) of rosuvastatin: the respective geometric least-square means increased by 7% (90% CI, 1.00–1.15) and 21% (90% CI, 1.14–1.28). The pharmacokinetic parameters of fenofibric acid were similar when fenofibrate was dosed alone and with rosuvastatin: the geometric least-square means for fenofibric acid AUC from 0 to 8 hours and Cmax decreased by 4% (90% CI, 0.90–1.02) and 9% (90% CI, 0.84–1.00), respectively. The treatments were well tolerated alone and in combination.Conclusion: Coadministration of rosuvastatin and fenofibrate produced minimal changes in rosuvastatin and fenofibric acid exposure.