{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:48:49Z","timestamp":1788925729632,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,10,22]],"date-time":"2013-10-22T00:00:00Z","timestamp":1382400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Amarin Pharma, Inc., Bedminster, NJ, USA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Icosapent ethyl (IPE) is a prescription form of eicosapentaenoic acid (EPA) ethyl ester. This randomized, open\u2010label study characterized EPA pharmacokinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four healthy subject groups received IPE for 28 days: three received 2\u2009g\/day (1\u2009\u00d7\u20091,000\u2009mg BID, 2\u2009\u00d7\u20091,000\u2009mg QD, or 2\u2009\u00d7\u2009500\u2009mg BID); one received 4\u2009g\/day (2\u2009\u00d7\u20091,000\u2009mg BID) administered with meals. Blood sampling was before the morning dose on days 1, 14, 26, 28, and at specified intervals during an 18\u2010day pharmacokinetic period. EPA was measured in plasma (total and unesterified) and red blood cells (RBCs) by liquid chromatography\/tandem mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean plasma total EPA increased from 19\u2009\u00b5g\/mL to a peak (C<jats:sub>max<\/jats:sub>) of 366\u2009\u00b5g\/mL at 5\u2009hours postdosing 4\u2009g\/day IPE on Day 28. Mean RBC EPA C<jats:sub>max<\/jats:sub> after 4\u2009g\/day was 89\u2009\u00b5g\/mL (baseline, 12\u2009\u00b5g\/mL). Mean steady state (SD) for half\u2010life, clearance, and volume of distribution of total EPA were 79 (47)\u2009hours, 757 (283)\u2009mL\/h, and 82 (56)\u2009L, respectively. Steady state for total and unesterified plasma EPA was reached by Day 28, whereas RBC levels were still increasing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>EPA pharmacokinetic profile demonstrated a slowly cleared, extensively distributed molecule with dose linearity and comparable exposures with BID and QD regimens.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cpdd.84","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T22:07:15Z","timestamp":1381529235000},"page":"101-108","source":"Crossref","is-referenced-by-count":54,"title":["Pharmacokinetics of eicosapentaenoic acid in plasma and red blood cells after multiple oral dosing with icosapent ethyl in healthy subjects"],"prefix":"10.1002","volume":"3","author":[{"given":"Rene A.","family":"Braeckman","sequence":"first","affiliation":[{"name":"Amarin Pharma, Inc. Bedminster NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Stirtan","sequence":"additional","affiliation":[{"name":"Amarin Pharma, Inc. Groton CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paresh N.","family":"Soni","sequence":"additional","affiliation":[{"name":"Amarin Pharma, Inc. Groton CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20040119"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e318235eb4d"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(01)01489-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-011-0210-3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2011.10.018"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2011.04.015"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.05.031"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/53.5.1185"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114599001737"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/58.3.360"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/83.6.1467S"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000142292.10048.B2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112261"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(88)80718-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(88)80937-9"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02533970"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/54.4.668"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-998-0188-8"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(93)90266-C"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02535864"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2012.01.002"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37132-7"},{"key":"e_1_2_8_24_1","unstructured":"Guidance for industry. Food\u2010effect bioavailability and fed bioequivalence studies. U.S. Department of Health and Human Services; Food and Drug Administration; Center for Drug Evaluation and Research. Available at:http:\/\/www.fda.gov\/downloads\/regulatoryinformation\/guidances\/ucm126833.pdf. 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