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.
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.
authors: Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors: Ryan M
authors: RM
authors: Franke
authors: Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors: Terri
authors: T
authors: Morton
authors: Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors: Krishna
authors: K
authors: Devarakonda
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D054796:Drug Dosage Calculations; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D010098:Oxycodone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019518:Postprandial Period; D016032:Randomized Controlled Trials as Topic; D013607:Tablets; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D013607:Tablets; C514822:oxycodone-acetaminophen; D000082:Acetaminophen; D010098:Oxycodone
keywords: acetaminophen; acute pain; biphasic; extended release; fixed-dose combination; immediate release; oxycodone; population pharmacokinetics