Effect of Concomitant Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) on the Pharmacokinetics of Atorvastatin

• Published in: Clinical drug investigation 2015-01, Vol.35 (1), p.45-51
• Main Authors: Braeckman, Rene A., Stirtan, William G., Soni, Paresh N.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Atorvastatin; Cross-Over Studies; Drug Interactions - physiology; Drug Therapy, Combination; Eicosapentaenoic Acid - administration & dosage; Eicosapentaenoic Acid - analogs & derivatives; Eicosapentaenoic Acid - pharmacokinetics; Female; Heptanoic Acids - administration & dosage; Heptanoic Acids - pharmacokinetics; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Original; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Pyrroles - administration & dosage; Pyrroles - pharmacokinetics; Treatment Outcome
• ISSN: 1173-2563; 1179-1918
• DOI: 10.1007/s40261-014-0252-8

Background and 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.