{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T20:49:54Z","timestamp":1772743794640,"version":"3.50.1"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,7,27]],"date-time":"2015-07-27T00:00:00Z","timestamp":1437955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100014468","name":"Mallinckrodt Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014468","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pain Practice"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine whether biphasic immediate\u2010release (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>)\/extended\u2010release (<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>) oxycodone (<jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content>)\/acetaminophen (<jats:styled-content style=\"fixed-case\">APAP<\/jats:styled-content>) 7.5\/325\u2010mg tablets have clinically relevant variability in population pharmacokinetics (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Post hoc analysis of 2 phase 1 randomized, open\u2010label, multiple\u2010dose crossover studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Single contract research organization clinic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects<\/jats:title><jats:p>Men and women aged 18 to 55\u00a0years with a body mass index of 19 to 30\u00a0kg\/m<jats:sup>2<\/jats:sup> and body weight \u2265\u00a059\u00a0kg.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fasted participants (<jats:italic>N<\/jats:italic>\u00a0=\u00a096) received 2 tablets of <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ER OC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">APAP<\/jats:styled-content> 7.5\/325\u00a0mg (total dose, 15\/650\u00a0mg) every 12\u00a0hours for 4.5\u00a0days. Population <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> analysis was performed using nonlinear mixed effects modeling and evaluated 6 population variables.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The average <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> estimates for <jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content> were 75\u00a0L\/hour for clearance (<jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content>\/<jats:italic>F<\/jats:italic>), 756\u00a0L for volume of distribution (<jats:italic>V<\/jats:italic>\/<jats:italic>F<\/jats:italic>), and 0.581\u00a0per hour for absorption rate constant (<jats:italic>K<\/jats:italic><jats:sub>a<\/jats:sub>). Body weight was a statistically significant source of variability in <jats:italic>V<\/jats:italic>\/<jats:italic>F<\/jats:italic> for <jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content> at steady state. Average estimates for <jats:styled-content style=\"fixed-case\">APAP<\/jats:styled-content> were 25\u00a0L\/hour for <jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content>\/<jats:italic>F<\/jats:italic> and 119\u00a0L for <jats:italic>V<\/jats:italic>\/<jats:italic>F<\/jats:italic>. Sex was identified as a statistically significant source of variability in <jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content>\/<jats:italic>F<\/jats:italic> with predicted values for <jats:styled-content style=\"fixed-case\">APAP<\/jats:styled-content> of 25\u00a0L\/hour in men and 21\u00a0L\/hour in women. Body weight affected variability in <jats:italic>V<\/jats:italic>\/<jats:italic>F<\/jats:italic>, with a predicted value of 193\u00a0L in men and 174\u00a0L in women for a 72\u2010kg participant at steady state.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Dose adjustments of &lt;\u00a050% are not clinically relevant for <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ER OC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">APAP<\/jats:styled-content> 7.5\/325\u2010mg tablets considering the approved dose of 1 to 2 tablets every 8 to 12\u00a0hours; thus, adjustment may be necessary for large deviations from normal body weight but not for sex.<\/jats:p><\/jats:sec>","DOI":"10.1111\/papr.12329","type":"journal-article","created":{"date-parts":[[2015,7,27]],"date-time":"2015-07-27T10:01:17Z","timestamp":1437991277000},"page":"730-736","source":"Crossref","is-referenced-by-count":3,"title":["Pooled Post Hoc Analysis of Population Pharmacokinetics of Oxycodone and Acetaminophen Following Multiple Oral Doses of Biphasic Immediate\u2010Release\/Extended\u2010Release Oxycodone\/Acetaminophen Tablets"],"prefix":"10.1111","volume":"16","author":[{"given":"Terri","family":"Morton","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Mallinckrodt Pharmaceuticals Hazelwood Missouri U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Franke","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Mallinckrodt Pharmaceuticals Hazelwood Missouri U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna","family":"Devarakonda","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Mallinckrodt Pharmaceuticals Hazelwood Missouri U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2007.04.013"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2005.11.003"},{"key":"e_1_2_6_4_1","first-page":"628284","article-title":"Pain prevalence and management in an internal medicine setting in Italy","volume":"2014","author":"Fabbian F","year":"2014","journal-title":"Pain Res Treat."},{"key":"e_1_2_6_5_1","unstructured":"OxyContin\u00ae(oxycodone HCl extended release tablets). 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