Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets
Ryan M Franke, Terri Morton, Krishna Devarakonda Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Abstract: This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetamin...
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Dove Medical Press
2015-08-01
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Series: | Drug Design, Development and Therapy |
Online Access: | http://www.dovepress.com/pooled-post-hoc-analysis-of-population-pharmacokinetics-of-oxycodone-a-peer-reviewed-article-DDDT |
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author | Franke RM Morton T Devarakonda K |
author_facet | Franke RM Morton T Devarakonda K |
author_sort | Franke RM |
collection | DOAJ |
description | Ryan M Franke, Terri Morton, Krishna Devarakonda Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Abstract: This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18–55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg. Participants received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or fed conditions. Six variables were examined: sex, race, age, weight, height, and body mass index. Single-dose population PK was analyzed using first-order conditional estimation methods. A total of 151 participants were included in the analysis under fasted conditions, and 31 participants were included in the fed analysis. Under fasted conditions, a 10% change in body weight was accompanied by ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC compared with white participants. Under fed conditions, the absorption rate constant of OC and APAP decreased significantly, although there was no effect on CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg tablets is two tablets every 12 hours, adjustments of <50% are not clinically relevant. Dose adjustment may be necessary for large deviations from average body weight, but the small PK effects associated with race and consumption of a meal are not clinically relevant. Keywords: acetaminophen, acute pain, biphasic, extended release, fixed-dose combination, immediate release, oxycodone, population pharmacokinetics |
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spelling | doaj.art-7e30e4602b7142d285df52eb75b565722022-12-22T01:27:07ZengDove Medical PressDrug Design, Development and Therapy1177-88812015-08-012015default4587459723079Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tabletsFranke RMMorton TDevarakonda KRyan M Franke, Terri Morton, Krishna Devarakonda Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Abstract: This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18–55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg. Participants received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or fed conditions. Six variables were examined: sex, race, age, weight, height, and body mass index. Single-dose population PK was analyzed using first-order conditional estimation methods. A total of 151 participants were included in the analysis under fasted conditions, and 31 participants were included in the fed analysis. Under fasted conditions, a 10% change in body weight was accompanied by ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC compared with white participants. Under fed conditions, the absorption rate constant of OC and APAP decreased significantly, although there was no effect on CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg tablets is two tablets every 12 hours, adjustments of <50% are not clinically relevant. Dose adjustment may be necessary for large deviations from average body weight, but the small PK effects associated with race and consumption of a meal are not clinically relevant. Keywords: acetaminophen, acute pain, biphasic, extended release, fixed-dose combination, immediate release, oxycodone, population pharmacokineticshttp://www.dovepress.com/pooled-post-hoc-analysis-of-population-pharmacokinetics-of-oxycodone-a-peer-reviewed-article-DDDT |
spellingShingle | Franke RM Morton T Devarakonda K Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets Drug Design, Development and Therapy |
title | Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets |
title_full | Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets |
title_fullStr | Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets |
title_full_unstemmed | Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets |
title_short | Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets |
title_sort | pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate release extended release oxycodone acetaminophen tablets |
url | http://www.dovepress.com/pooled-post-hoc-analysis-of-population-pharmacokinetics-of-oxycodone-a-peer-reviewed-article-DDDT |
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