Effects of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) on Pharmacokinetic Parameters of Rosiglitazone in Healthy Subjects

BACKGROUND: Icosapent ethyl is a high-purity form of eicosapentaenoic acid ethyl ester approved to reduce triglyceride levels in adults with triglycerides ≥500 mg/dL. Candidates for triglyceride-lowering therapy include patients with diabetes mellitus who may be receiving rosiglitazone. We assessed the effects of icosapent ethyl on the pharmacokinetic parameters of rosiglitazone. METHODS: Subjects received a single 8-mg oral dose of rosiglitazone alone and with oral icosapent ethyl 4 g/day in this open-label drug–drug interaction study. Pharmacokinetic end points included area under the concentration versus time curve from time zero to infinity (AUC(0–inf)) and maximum observed concentration (C(max)) for rosiglitazone with and without icosapent ethyl. RESULTS: Of 30 subjects enrolled, 28 completed the study. Icosapent ethyl 4 g/day at steady-state did not significantly change the single-dose AUC(0–inf) or C(max) of rosiglitazone 8 mg. Least squares geometric mean ratios (90% confidence interval) for AUC(0–inf) and C(max) of rosiglitazone given with icosapent ethyl versus rosiglitazone alone were 0.90 (87.00–93.40) and 1.01 (92.02–109.9), respectively. No serious adverse events were reported and no subject discontinued due to an adverse event. CONCLUSIONS: At steady-state concentrations, icosapent ethyl did not inhibit the pharmacokinetics of rosiglitazone. Co-administration of icosapent ethyl and rosiglitazone was safe and well tolerated.