Intra- and interindividual variability of glucuronidation of paracetamol during repeated administration of propacetamol in neonates
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Background: Major changes in drug clearance and metabolism are observed during infancy, in part based on ontogenic regulation of various metabolic pathways. Since paracetamol provides a good substrate to study UGT (1A6) activity, urinary metabolites of propacetamol were determined in neonates in whom propacetamol was repeatedly administered. Methods: Paracetamol glucuronide (APAP-G), paracetamol sulphate (APAP-S) and free paracetamol were determined in urine samples of neonates during repeated administration of propacetamol. Spearman rank and linear multiple regression (MedCalc®, Mariakerke, Belgium) were used to study the effect of postnatal age, of postconceptional age and of repeated administration on the relative contribution of APAP-G to overall urine paracetamol (APAP-G + APAP-S + free paracetamol) elimination (G/T ratio). Results: 147 samples were collected in 23 neonates. Molar median G/T ratio was 14% (range 1-53). Besides increasing G/T ratio with increasing postnatal (p<0.0001) and postconceptional age (p<0.01), repeated administration (p<0.01) also correlated with an increasing G/T ratio, and repeated administration remained significant (p<0.01) after correction of postnatal and postconceptional age in a multiple regression model. Conclusion: Major variability in the ontogeny of UGT activity to overall elimination of paracetamol was documented in neonates. Besides postnatal and postconceptional age, a significant effect of repeated administration on UGT activity was documented.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.003 |
| 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 it