BackgroundIcosapent 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.MethodsSubjects 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.ResultsOf 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.ConclusionsAt steady-state concentrations, icosapent ethyl did not inhibit the pharmacokinetics of rosiglitazone. Co-administration of icosapent ethyl and rosiglitazone was safe and well tolerated.