Effect of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) on Omeprazole Plasma Pharmacokinetics in Healthy Adults

Abstract

Background: Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved by the US Food and Drug Administration as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia. Patients with high serum triglycerides may be taking concurrent medications for associated conditions such as obesity and/or diabetes mellitus. Objective: To evaluate the effect of IPE on the plasma pharmacokinetics (PK) of omeprazole, a commonly used proton pump inhibitor and a substrate of cytochrome P450 (CYP) 2C19. Study design: Omeprazole (40 mg/day for 7 days) was administered orally without and with 4 g/day IPE at steady state. The primary PK endpoint was area under the concentration-time curve from time 0 to 24 h (AUC 0–24); secondary endpoints included maximum observed plasma concentration (C max). Safety was monitored in all subjects who received one or more dose(s) of the study drug. Participants: Thirty healthy adult subjects were enrolled and 28 completed the study. Results: IPE 4 g/day at steady state did not significantly change the AUC 0–24 or C max of omeprazole when co-administered at 40 mg/day to steady state. The ratios of least squares geometric means (90 % confidence interval) for AUC 0–24 and C max (omeprazole with IPE vs. omeprazole alone) were 0.84 (76.0–91.9) and 1.01 (87.4–116.3), respectively. There were no clinically significant findings from laboratory tests, vital signs, or physical examinations. Conclusions: At steady-state concentrations, IPE 4 g/day did not inhibit the AUC 0–24 or C max of omeprazole 40 mg/day, a CYP2C19 substrate. Co-administration of IPE with omeprazole was safe and well tolerated.