Pooled Post Hoc Analysis of Population Pharmacokinetics of Oxycodone and Acetaminophen Following Multiple Oral Doses of Biphasic Immediate‐Release/Extended‐Release Oxycodone/Acetaminophen Tablets
Bibliographic record
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 (Ka ). 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.010 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".