Pharmacokinetics and safety of tadalafil in a paediatric population with pulmonary arterial hypertension: A multiple ascending‐dose study
Bibliographic record
Abstract
Aims To evaluate the pharmacokinetics and safety of once‐daily (QD) tadalafil in paediatric patients with pulmonary arterial hypertension (PAH) to establish an appropriate dose range for further research. Methods This was an open‐label, multicentre, international, multiple‐ascending‐dose study. Patients aged ≥2 years were enrolled into 1 of 3 cohorts based on body weight: heavy‐weight (≥40 kg), middle‐weight (25 to <40 kg), and light‐weight (<25 kg). Each patient received tadalafil QD for 10 weeks: 5 weeks at a low dose, then 5 weeks at a high dose. The doses for each cohort were intended to produce plasma tadalafil concentrations within the range produced by 5–10 mg (for the low dose) or 20–40 mg (for the high dose) of tadalafil in adults with PAH. Area under the plasma concentration–time curve during 1 dosing interval (AUC τ ), maximum concentration, and apparent clearance were assessed throughout the trial, as were safety and tolerability. Results The study enrolled 19 patients aged 2–17 years, weighing 9.9–76.0 kg. Tadalafil's median (range) steady‐state AUC τ at the high dose was 7243 (3131–13 088) ng•h/mL across all patients. Concentrations were higher in no bosentan‐treated patients than in bosentan‐treated patients, but both populations were within the range of respective adult patients taking 20–40 mg QD. Tadalafil had an acceptable safety profile consistent with the known safety profile of tadalafil in adults. Conclusions Tadalafil 40 mg QD for patients ≥40 kg, and 20 mg QD for patients <40 kg and aged ≥2 years, are suitable for further research in paediatric patients with PAH.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".