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 (AUC0-inf) and maximum observed concentration (Cmax) 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 AUC0-inf or Cmax of rosiglitazone 8 mg. Least squares geometric mean ratios (90% confidence interval) for AUC0-inf and Cmax 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.