Midazolam Metabolism: Implications for Individualised Dosing?
Bibliographic record
Abstract
ABSTRACT Aim To compare the clearance of midazolam and its metabolites in critically ill paediatric and adult patients. Method A prospective study conducted in paediatric and adult intensive care units. Patients over 2 years of age receiving midazolam for therapeutic sedation were eligible for enrolment. Midazolam and its metabolite concentrations were determined in plasma and urine. Results The median (interquartile range) steady‐state concentrations observed in the paediatric and adult groups were 90 mg/L (48–135) and 253 mg/L (148–404), respectively (p = 0.90). The median daily doses were 1.8 mg/kg (0.6–2.2) and 1.9 mg/kg (0.6–2.7), respectively (p = 0.84). Midazolam clearance in paediatric and adult patients was 1.1 mL/kg/min (0.9–3.8) and 2.9 mL/kg/min (0.9–3.8), respectively. Analysis of clearances by age identified two peaks in midazolam and its metabolites occurring around 12 years of age and at 45 years of age. Neither midazolam nor its metabolites appeared to accumulate in blood after long courses of treatment (> 3 days). Conclusion A conclusion that could be drawn from this study is that some of midazolam's pharmacokinetic variability may be explained by age‐related changes in metabolism. These findings require validation in a larger study.
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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 | 0.006 | 0.025 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".