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Population Pharmacokinetics and Pharmacodynamics of Vancomycin in Pediatric Patients With Various Degrees of Renal
Chanika Chuphan1, Waroonrat Sukarnjanaset2, Thanyawee Puthanakit3
1Department of Pharmacy Practice (CC, TW), Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Insights
Optimized vancomycin dosing for pediatric patients with methicillin-resistant Staphylococcus aureus (MRSA) infection is crucial. This study suggests specific daily dosages based on estimated glomerular filtration rates (eGFR) to improve treatment efficacy and reduce toxicity.
Area of Science:
- Pharmacology
- Pediatric Infectious Diseases
- Nephrology
Background:
- Current vancomycin dosing guidelines for pediatric MRSA infections may lead to inadequate exposure or toxicity.
- Individualized dosing is necessary, especially considering varying degrees of renal function in children.
Purpose of the Study:
- To explore optimal vancomycin dosing strategies for pediatric patients with MRSA infections.
- To correlate vancomycin dosage with pharmacokinetic targets (AUC0-24 hr/MIC) across different levels of renal function.
Main Methods:
- Retrospective analysis of routine monitoring data from pediatric patients (1 month to 18 years).
- Population pharmacokinetic (PK) analysis using NONMEM and Monte Carlo simulation via Crystal Ball software.
- Inclusion of 212 patients with 348 vancomycin serum concentrations and a wide range of eGFRs.
Main Results:
- A 1-compartment model with first-order elimination adequately described vancomycin PK.
- Recommended daily vancomycin doses (mg/kg/day) for target AUC0-24 hr/MIC ≥400 and <800 mg•h/L were determined for specific eGFR ranges (15-29, 30-59, 60-89, 90-129, 130-160 mL/min/1.73 m²).
- These suggested doses achieved >85% cumulative fraction of response across MRSA MIC distributions.
Conclusions:
- Specific vancomycin dosages are proposed for pediatric patients based on their eGFR.
- These recommendations aim to optimize therapeutic outcomes for MRSA infections while minimizing toxicity.
- The findings support tailored vancomycin dosing in pediatric populations with impaired renal function.
Objective:
Although vancomycin dosage recommendations in the pediatric setting for methicillin-resistant Staphylococcus aureus (MRSA) infection indicate that ≥60 mg/kg/day is correlated to a desired area under the vancomycin concentration time curve from 0 to 24 hours to minimum inhibitory concentration ratio (AUC0-24 hr/MIC) ≥400, for some patients this dosage is inadequate or relates to toxicity. This study purposed to explore vancomycin dosing for pediatrics with various degrees of renal function.
Methods:
Routine monitoring data were retrospectively collected from patients, aged 1 month to 18 years. Population pharmacokinetic analysis was performed by using non-linear mixed-effect model with NONMEM software, and Monte Carlo simulation was conducted by using Crystal Ball software.
Results:
Two hundred twelve patients with 348 vancomycin serum concentrations were included. Median age was 3.5 years (IQR, 0.9-10.9), median weight was 14.0 kg (IQR, 7.2-30.4), with baseline estimated glomerular filtration rate (eGFR) ranging from 15.5 to 359.3 mL/min/1.73 m2. A 1-compartment model with first-order elimination sufficiently described vancomycin PK. The dosing targeting AUC0-24hr/MIC ≥400 and AUC0-24hr <800 mg•h/L for pediatric patients with eGFRs of 15 to 29, 30 to 59, 60 to 89, 90 to 129, and 130 to 160 mL/min/1.73 m2 was 12.5, 25, 40, 60, and 70 mg/kg/day, respectively. All vancomycin dosing obtained >85% of the cumulative fraction of response across the MIC distribution of MRSA.
Conclusions:
Vancomycin dosing of 12.5, 25, 40, 60, and 70 mg/kg/day is suggested for pediatric patients with eGFRs of 15 to 29, 30 to 59, 60 to 89, 90 to 129, and 130 to 160 mL/min/1.73 m2, respectively.
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