title: Icosapent ethyl: Eicosapentaenoic acid concentration and triglyceride-lowering effects across clinical studies.
abstract: Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved at a dose of 4g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500mg/dL) hypertriglyceridemia. This post-hoc exploratory analysis examined the relationship of icosapent ethyl dose with EPA concentrations in plasma and red blood cells (RBCs) across 3 clinical studies-a phase 1 pharmacokinetic study in healthy adult volunteers and 2 pivotal phase 3 studies (MARINE and ANCHOR) in adult patients with hypertriglyceridemia-and examined the relationship between EPA levels and TG-lowering effects in MARINE and ANCHOR. In all 3 studies, icosapent ethyl produced dose-dependent increases in the concentrations of EPA in plasma and RBCs. In both MARINE and ANCHOR, these dose-dependent EPA increases correlated with the degree of TG level lowering (all P<0.01). In patients with high TG levels (≥200mg/dL) and treated with icosapent ethyl 4g/day, the end-of-treatment plasma and RBC EPA concentrations were >170μg/mL and>70μg/mL, respectively. These studies support icosapent ethyl as producing predictable dose-dependent pharmacokinetics/pharmacodynamics, with TG level lowering dependent upon icosapent ethyl dose and EPA concentrations in plasma and RBCs.
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA. Electronic address: hbaysmd@aol.com.
authors.forename: Harold E
authors.initials: HE
authors.lastname: Bays
authors.affiliation: Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, 6565 Fannin, M.S. A-601, Houston, TX 77030, USA. Electronic address: cmb@bcm.tmc.edu.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ 07921, USA. Electronic address: ralph.doyle@amarincorp.com.
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Doyle
authors.affiliation: Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ 07921, USA. Electronic address: rebecca.juliano@amarincorp.com.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Juliano
authors.affiliation: Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ 07921, USA. Electronic address: sephy.philip@amarincorp.com.
authors.forename: Sephy
authors.initials: S
authors.lastname: Philip
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood*
chemical_list: D000960:Hypolipidemic Agents; D014280:Triglycerides; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid
keywords: Eicosapentaenoic acid; Hypertriglyceridemia; Icosapent ethyl; Pharmacodynamics; Triglycerides