Oral morphine pharmacokinetics in healthy children and the effect of genetic polymorphisms: An exploratory study
Bibliographic record
Abstract
ABSTRACT Objectives To explore the pharmacokinetics of oral morphine and the potential effect of pharmacogenetics on efficacy and safety in children. Methods Serial blood samples were obtained from healthy children aged 5–17 years. We determined morphine, morphine-6-glucoronide (M6G) and morphine-3-glucoronide (M3G) concentrations and pharmacokinetic parameters. We performed genotyping and collected pain scores. Results A total of 13 children received a single dose of oral morphine 0.5 mg/kg. For morphine, M6G, and M3G, median Tmax was 52.5, 90, and 90 min, respectively. Median Cmax reached 14.07, 53.64, and 309.63 ng/mL, respectively. Median t1/2 was 74.96, 170.73, and 149.45 min, respectively. Median area under the curve was 1757.71, 3290.83, and 43618.97 ng*h/mL, respectively. A single nucleotide polymorphism rs563649 on the OPRMI gene locus was associated with reduced receptor efficiency in one patient reporting an increase in pain. Conclusions Oral morphine’s active metabolites have a longer t1/2 and an OPMR1 SNP rs563649 may underlie variability in efficacy and safety. Clinical Trials Registration: clinicaltrials.gov NCT01690780.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".