title: Effect of concomitant icosapent ethyl (eicosapentaenoic acid ethyl ester) on the pharmacokinetics of atorvastatin.
abstract: OBJECTIVE
  Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved as an adjunct to diet to reduce triglyceride levels in adult patients with triglyceride levels ≥500 mg/dL (≥5.65 mmol/L). The objective of this open-label, drug-drug interaction study was to examine the effects of icosapent ethyl on the steady-state pharmacokinetics of atorvastatin, a commonly prescribed medication in patients with dyslipidaemia.
  
  
  METHODS
  Thirty healthy subjects received atorvastatin 80 mg/day on days 1-7, icosapent ethyl 4 g/day on days 8-28, and co-administration on days 29-35. Primary end-points were natural log-transformed maximum plasma concentration (C(max)) and area under the concentration-versus-time curve from 0 to 24 h (AUC(0-24)) for atorvastatin, 2-hydroxyatorvastatin, and 4-hydroxyatorvastatin with and without icosapent ethyl.
  
  
  RESULTS
  Of the 30 subjects enrolled, 26 completed the study. The 90% confidence intervals for C(max) and AUC(0-24) least-squares geometric mean ratios were within the 0.80-1.25 bounds. Concomitant administration of icosapent ethyl and atorvastatin was safe and well tolerated and icosapent ethyl did not significantly change the steady state C(max) and AUC(0-24) of atorvastatin, 2-hydroxyatorvastatin, or 4-hydroxyatorvastatin.
  
  
  CONCLUSIONS
  At steady-state concentrations, icosapent ethyl did not have an effect on the pharmacokinetics of atorvastatin. Co-administration of icosapent ethyl and atorvastatin was safe and well tolerated in healthy adult subjects.
authors.affiliation: Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ, 07921, USA.
authors.forename: Rene A
authors.initials: RA
authors.lastname: Braeckman
authors.forename: William G
authors.initials: WG
authors.lastname: Stirtan
authors.forename: Paresh N
authors.initials: PN
authors.lastname: Soni
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000069059:Atorvastatin; D018592:Cross-Over Studies; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D006538:Heptanoic Acids; D011758:Pyrroles; C035276:eicosapentaenoic acid ethyl ester; D000069059:Atorvastatin; D015118:Eicosapentaenoic Acid