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Initial Dosage Recommendation for Sirolimus in Children With Tuberous Sclerosis Complex
Dong-Dong Wang1, Xiao Chen1, Hong Xu2
1Department of Pharmacy, Children's Hospital of Fudan University, Shanghai, China.
Frontiers in Pharmacology
|June 30, 2020
Summary
This study recommends optimal initial sirolimus dosing regimens for children with tuberous sclerosis complex (TSC). The findings provide crucial guidance for pediatric sirolimus treatment, addressing variability in drug concentration.
Area of Science:
- Pharmacology
- Pediatrics
- Genetics
Background:
- Sirolimus is used for tuberous sclerosis complex (TSC) but has a narrow therapeutic range.
- Significant pharmacokinetic variability complicates initial dosing, especially in pediatric TSC patients.
Purpose of the Study:
- To establish optimal sirolimus initial dosing regimens for pediatric patients with TSC.
- To address challenges in sirolimus therapy due to pharmacokinetic variability in children.
Main Methods:
- Utilized a nonlinear mixed-effects (NONMEM) model to analyze physiological and genetic factors affecting sirolimus concentrations.
- Employed Monte Carlo simulations to determine optimal dosing strategies.
- Collected data on underlying physiological and genetic factors influencing sirolimus levels.
Main Results:
- Recommended specific once-daily sirolimus dosages based on weight for pediatric TSC patients (e.g., 0.10 mg/kg/day for 5-10 kg).
- Recommended specific twice-daily sirolimus dosages based on weight for pediatric TSC patients (e.g., 0.04 mg/kg/day for 5-20 kg).
- These represent the first-ever recommended initial sirolimus dosages for children with TSC.
Conclusions:
- The study provides evidence-based, weight-tiered dosing recommendations for sirolimus in pediatric TSC.
- These regimens aim to optimize therapeutic outcomes by managing sirolimus pharmacokinetic variability.
- The findings facilitate safer and more effective sirolimus initiation in children with TSC.
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