Abstract: SA-PO0677
Beyond Weight-Based Dosing: In Silico Modeling Reveals Effect of Kidney Maturation on Gentamicin Exposure in Infants
Session Information
- Pediatric Nephrology: Transplantation, Hypertension, AKI, Genetics, and Developmental Diseases
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Meigel, Felix J., Renal Research Institute, New York, New York, United States
- Alvarez-Elias, Ana Catalina, Fresenius Medical Care, Clinical Research, New York, New York, United States
- Hussein, Rasha, Fresenius Medical Care, Clinical Research, New York, New York, United States
- Fuertinger, Doris H., Renal Research Institute, New York, New York, United States
Background
In pediatric dosing, age and anthropometrics like weight and height are used to adjust for physiological maturity but fall short in capturing inter-individual variability (IIV) in renal development, which may arise from prematurity, low birth weight, or acute illness—altering drug exposure. Aminoglycosides, which are renally cleared, require high peaks for efficacy but pose nephrotoxicity risks. Using in silico modeling, we assessed how renal function and weight separately affect gentamicin exposure in neonates and infants.
Methods
We simulated gentamicin exposure in 20,000 virtual patients (age: 1 day–2 years), based on a meta-analysis of both published pediatric pharmacokinetic models and published GFR measurements. Anthropometrics were sampled from WHO growth standards. Patients were divided into age-homogeneous cohorts (1 day; 2, 6, and 24 months; N=5,000 each, equal sex distribution). A two-compartment model simulated standard weight-adjusted dosing: 5 mg/kg q36h for neonates, 7 mg/kg q24h for older infants. Within cohorts, normalized GFR and weight were independently varied ±20% to evaluate their impact on exposure.
Results
All age cohorts showed substantial IIV. At baseline, the proportion exceeding recommended trough thresholds (>1.0 mg/L for neonates, >0.5 mg/L for older infants) was 79.0% (1 day), 60.8% (2 months), 19.5% (6 months), and 1.1% (24 months). Both weight and GFR changes increased trough exceedance, with reduced GFR having a greater impact. A 20% weight increase raised these values to 83.6%, 74.4%, 33.1%, and 4.7%, respectively. In contrast, a 20% GFR reduction increased them more markedly to 92.7%, 93.3%, 65.5%, and 23.6%. Peak levels remained stable, varying <5% across all scenarios.
Conclusion
Renal function deviations had a greater impact on gentamicin exposure than weight changes. High IIV even in age-homogeneous cohorts reinforces the importance of therapeutic drug monitoring from treatment start. In silico population modeling emerges as a valuable tool to educate on IIV and support safer pediatric dosing.
Funding
- Commercial Support – Fresenius Medical Care Deutschland GmbH