Pooled Post Hoc Analysis of Population Pharmacokinetics of Oxycodone and Acetaminophen Following Multiple Oral Doses of Biphasic Immediate‐Release/Extended‐Release Oxycodone/Acetaminophen Tablets. Issue 6 (27th July 2015)

• Record Type: Journal Article
• Authors: Morton, Terri; Franke, Ryan; Devarakonda, Krishna
• Is Part Of: Pain practice. Volume 16:Issue 6(2016:Jul.)
• Page Start: 730
• Page End: 736
• Publication Date: 2015-07-27
• Subjects: acetaminophen -- acute pain -- extended release -- fixed‐dose combination -- population pharmacokinetics -- oxycodone -- opioid analgesic; Pain -- Treatment -- Periodicals; 616.0472
• DOI: 10.1111/papr.12329
• Languages: English
• ISSNs: 1530-7085

Abstract

Abstract: Objective: To examine whether biphasic immediate‐release (IR)/extended‐release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325‐mg tablets have clinically relevant variability in population pharmacokinetics (PK). Design: Post hoc analysis of 2 phase 1 randomized, open‐label, multiple‐dose crossover studies. Setting: Single contract research organization clinic. Subjects: Men and women aged 18 to 55 years with a body mass index of 19 to 30 kg/m 2 and body weight ≥ 59 kg. Methods: Fasted participants ( N = 96) received 2 tablets of IR/ER OC/APAP 7.5/325 mg (total dose, 15/650 mg) every 12 hours for 4.5 days. Population PK analysis was performed using nonlinear mixed effects modeling and evaluated 6 population variables. Results: The average PK estimates for OC were 75 L/hour for clearance (CL/ F ), 756 L for volume of distribution ( V / F ), and 0.581 per hour for absorption rate constant ( K a ). Body weight was a statistically significant source of variability in V / F for OC at steady state. Average estimates for APAP were 25 L/hour for CL/ F and 119 L for V / F . Sex was identified as a statistically significant source of variability in CL/ F with predicted values for APAP of 25 L/hour in men and 21 L/hour in women. Body weight affected variability in V / F, with a predicted value of 193 L in men and 174 L in women for a 72‐kg participant at steady state. Conclusions: Dose adjustments of < 50% are not clinically relevant for IR/ER OC/APAP 7.5/325‐mg tablets considering the approved dose of 1 to 2 tablets every 8 to 12 hours; thus, adjustment may be necessary for large deviations from normal body weight but not for sex.