{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T05:10:41Z","timestamp":1769836241498,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,10,15]],"date-time":"2013-10-15T00:00:00Z","timestamp":1381795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:sec><jats:title>Study Objective<\/jats:title><jats:p>To characterize the effects of two doses (10 and 60\u00a0mg) of lomitapide\u2014a microsomal triglyceride transfer protein inhibitor approved as adjunct treatment to lower low\u2010density lipoprotein cholesterol levels in patients with homozygous familial hypercholesterolemia\u2014on the pharmacokinetics of several lipid\u2010lowering therapies: atorvastatin, simvastatin, rosuvastatin, fenofibrate, ezetimibe, and niacin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Two prospective open\u2010label studies (study 1 and study 2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Two clinical research units.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects<\/jats:title><jats:p>A total of 130 healthy volunteers (114 subjects in study 1 and 16 subjects in study 2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>In study 1, subjects were enrolled sequentially to one of the following eight open\u2010label treatment arms (probe drug\u00a0+\u00a0lomitapide): atorvastatin 20\u00a0mg\u00a0+\u00a0lomitapide 10\u00a0mg, atorvastatin 20\u00a0mg\u00a0+\u00a0lomitapide 60\u00a0mg, simvastatin 20\u00a0mg\u00a0+\u00a0lomitapide 10\u00a0mg, rosuvastatin 20\u00a0mg\u00a0+\u00a0lomitapide 10\u00a0mg, rosuvastatin 20\u00a0mg\u00a0+\u00a0lomitapide 60\u00a0mg, fenofibrate 145\u00a0mg\u00a0+\u00a0lomitapide 10\u00a0mg, ezetimibe 10\u00a0mg\u00a0+\u00a0lomitapide 10\u00a0mg, and extended\u2010release niacin 1000\u00a0mg\u00a0+\u00a0lomitapide 10\u00a0mg. Study 2 consisted of the ninth treatment arm: simvastatin 40\u00a0mg\u00a0+\u00a0lomitapide 60\u00a0mg. Subjects received one dose of the probe drug on the morning of day 1. On days 2\u20137, subjects took their dose of lomitapide once\/day in the morning. On day 8, subjects received one dose of lomitapide simultaneously with the same probe drug they took on day 1. Subjects returned 1\u00a0week later (day 15) for a final visit to check safety laboratory parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements and Main Results<\/jats:title><jats:p>A full pharmacokinetic profile was performed for the probe drug on day 1 and day 8 (after 7\u00a0days of dosing with lomitapide [i.e., at steady state]). Pharmacokinetic parameters were calculated from the plasma concentration\u2010time data for each day by using noncompartmental methods. Analysis of variance was applied to the ln\u2010transformed maximum concentration (C<jats:sub>max<\/jats:sub>) and area under the plasma concentration\u2010time curve from time 0\u2013t (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>0\u2013t<\/jats:sub>) values, and ratios of the means were compared for day 8 versus day 1. Lomitapide increased exposure to the statin medications. The percent least squares means ratios (<jats:styled-content style=\"fixed-case\">LSMR<\/jats:styled-content>%) (90% confidence intervals [<jats:styled-content style=\"fixed-case\">CIs<\/jats:styled-content>]) for <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>0\u2013t<\/jats:sub> of the statin medications with lomitapide at the 60\u00a0mg dose were as follows: 129 (115\u2013144) for the sum of the active atorvastatin moieties, 168 (139\u2013203) for simvastatin acid, and 132 (112\u2013157) for rosuvastatin. The <jats:styled-content style=\"fixed-case\">LSMR<\/jats:styled-content>% (90% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) for C<jats:sub>max<\/jats:sub> was 138 (120\u2013160) for the sum of the active atorvastatin moieties, 157 (133\u2013186) for simvastatin acid, and 104 (82\u201332) for rosuvastatin. The <jats:styled-content style=\"fixed-case\">LSMR<\/jats:styled-content>s were not appreciably altered for the other probe drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study shows that lomitapide is a weak inhibitor of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 and increased the exposure of statin medications. Careful monitoring of adverse events of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4\u2010metabolized statins should be used when initiating therapy with lomitapide.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1351","type":"journal-article","created":{"date-parts":[[2013,10,15]],"date-time":"2013-10-15T12:31:53Z","timestamp":1381840313000},"page":"227-239","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Pharmacokinetic Interactions of the Microsomal Triglyceride Transfer Protein Inhibitor, Lomitapide, with Drugs Commonly Used in the Management of Hypercholesterolemia"],"prefix":"10.1002","volume":"34","author":[{"given":"Sony","family":"Tuteja","sequence":"first","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics University of Pennsylvania School of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Duffy","sequence":"additional","affiliation":[{"name":"Jefferson Medical College Division of Cardiology Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard L.","family":"Dunbar","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics University of Pennsylvania School of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajesh","family":"Movva","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics University of Pennsylvania School of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram","family":"Gadi","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics University of Pennsylvania School of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LeAnne T.","family":"Bloedon","sequence":"additional","affiliation":[{"name":"Aegerion Pharmaceuticals Inc. 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