Pharmacokinetics of Eicosapentaenoic Acid in Plasma and Red Blood Cells After Multiple Oral Dosing With Icosapent Ethyl in Healthy Subjects.

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Braeckman RA, Stirtan WG, Soni PN

Pharmacokinetics of Eicosapentaenoic Acid in Plasma and Red Blood Cells After Multiple Oral Dosing With Icosapent Ethyl in Healthy Subjects.

Clin Pharmacol Drug Dev. 2014 Mar;3(2):101-108. Epub 2013 Oct 22.

PubMed ID
26097787 [ View in PubMed
]
Abstract

OBJECTIVE: Icosapent ethyl (IPE) is a prescription form of eicosapentaenoic acid (EPA) ethyl ester. This randomized, open-label study characterized EPA pharmacokinetics. METHODS: Four healthy subject groups received IPE for 28 days: three received 2 g/day (1 x 1,000 mg BID, 2 x 1,000 mg QD, or 2 x 500 mg BID); one received 4 g/day (2 x 1,000 mg BID) administered with meals. Blood sampling was before the morning dose on days 1, 14, 26, 28, and at specified intervals during an 18-day pharmacokinetic period. EPA was measured in plasma (total and unesterified) and red blood cells (RBCs) by liquid chromatography/tandem mass spectrometry. RESULTS: Mean plasma total EPA increased from 19 microg/mL to a peak (Cmax) of 366 microg/mL at 5 hours postdosing 4 g/day IPE on Day 28. Mean RBC EPA Cmax after 4 g/day was 89 microg/mL (baseline, 12 microg/mL). Mean steady state (SD) for half-life, clearance, and volume of distribution of total EPA were 79 (47) hours, 757 (283) mL/h, and 82 (56) L, respectively. Steady state for total and unesterified plasma EPA was reached by Day 28, whereas RBC levels were still increasing. CONCLUSIONS: EPA pharmacokinetic profile demonstrated a slowly cleared, extensively distributed molecule with dose linearity and comparable exposures with BID and QD regimens.

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