title: 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.
  
  
  METHODS
  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 (AUC0-24); 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.
  
  
  METHODS
  Thirty healthy adult subjects were enrolled and 28 completed the study.
  
  
  RESULTS
  IPE 4 g/day at steady state did not significantly change the AUC0-24 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 AUC0-24 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 AUC0-24 or C max of omeprazole 40 mg/day, a CYP2C19 substrate. Co-administration of IPE with omeprazole was safe and well tolerated.
authors: Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ, 07921, USA.
authors: Rene A
authors: RA
authors: Braeckman
authors: William G
authors: WG
authors: Stirtan
authors: Paresh N
authors: PN
authors: Soni
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19 / Q000378:metabolism; D004347:Drug Interactions; D015118:Eicosapentaenoic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000494:pharmacology*; D008875:Middle Aged; D009853:Omeprazole / Q000009:adverse effects / Q000493:pharmacokinetics*; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000960:Hypolipidemic Agents; D054328:Proton Pump Inhibitors; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole