Enzyme Replacement in Fabry Disease: Pharmacokinetics and Pharmacodynamics of Agalsidase Alfa in Children and Adolescents
Bibliographic record
Abstract
This multicenter, open-label study evaluated pharmacokinetics, pharmacodynamics, and safety of agalsidase alpha in pediatric compared with adult patients with Fabry disease. The pharmacokinetic parameters of pediatric patients (19 boys, 5 girls, 6-18 years old; mean age, 11.8 years) were compared to those of adult male and female patients who participated in other clinical studies. All patients received agalsidase alpha at a dose of 0.2 mg/kg infused over 40 minutes every other week. Agalsidase alpha exhibited a biphasic serum elimination profile with a maximum serum concentration at the end of the 40-minute infusion; <1% of the maximum concentration was detected 8 hours after dosing. In children, serum clearance was 2.0 to 9.4 mL/min/kg and tended to decrease with increasing age. The average clearance in children, 3.7 +/- 1.5 mL/min/kg (mean +/- SD), was significantly greater than that measured in 33 adults (2.3 +/- 0.7 mL/min/kg, P < .0001). Mean terminal elimination half-life of agalsidase alpha was prolonged in week 25 compared with baseline (150 vs 66 minutes) in 8 of 19 male children. The magnitude of the reduction of plasma globotriaosylceremide was similar in all age groups and was independent of area under the curve and other pharmacokinetic parameters. Except for clearance in younger patients, agalsidase alpha appears to have comparable pharmacokinetic and pharmacodynamic profiles in pediatric and adult Fabry patients of both genders.
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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 | 0.001 |
| 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 | 0.000 | 0.000 |
| 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 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".