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.

Gender Variations in Pharmacokinetics of Paracetamol in Hausa/Fulani Ethnic group in Northwest Nigeria – A Two-stage Approach

“…Our findings on clearance and apparent volume of distribution were quite lower when compared to the values documented by other workers. [ 28 ] Despite variation in the study participants and geography, our findings were close to the ones reported in previous studies. [ 29 30 ] This observation has reechoed the variability in the pharmacokinetics of acetaminophen within and between populations.…”

Impact of Gastrointestinal Surgery on Absorption of Oxycodone: Experimental studies in patients with Roux-en-Y gastric bypass and short bowel syndrome

“…To evaluate the pharmacokinetics of the different oxycodone formulations, venous blood samples were collected before and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.33, 2.66, 3, 3.33, 3.66, 4, 5, 6, 8, 12 and 24 h after drug administration. These sampling times were chosen to best capture the pharmacokinetic profile of oxycodone and were based on previously conducted pharmacokinetic studies (11,38,(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69). Plasma concentrations of oxycodone, noroxycodone and oxymorphone were determined using highperformance liquid chromatography.…”