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Pooled Post Hoc Analysis of Population Pharmacokinetics of Oxycodone and Acetaminophen Following Multiple Oral Doses of Biphasic Immediate‐Release/Extended‐Release Oxycodone/Acetaminophen Tablets
Author(s) -
Morton Terri,
Franke Ryan,
Devarakonda Krishna
Publication year - 2016
Publication title -
pain practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 58
eISSN - 1533-2500
pISSN - 1530-7085
DOI - 10.1111/papr.12329
Subject(s) - oxycodone , medicine , acetaminophen , pharmacokinetics , post hoc analysis , anesthesia , immediate release , post hoc , pharmacology , population , opioid , receptor , environmental health
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.