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Published on: September 10, 2018
Population Pharmacokinetic Analysis and Dose Regimen Optimization in Japanese Infants with an Extremely Low Birth
Hiroshi Sasano1,2, Kanon Aoki2, Ryutarou Arakawa3
1Department of Pharmacy, Juntendo University Hospital, Tokyo, Japan hsasano@juntendo.ac.jp.
Insights
Vancomycin dosing for extremely low-birth-weight infants needs adjustment. This study developed a pharmacokinetic model to optimize vancomycin dosage, finding lower doses are necessary for this vulnerable population.
Area of Science:
- Neonatal Pharmacology
- Antibiotic Pharmacokinetics
- Pediatric Infectious Diseases
Background:
- Vancomycin is crucial for Gram-positive infections.
- Limited pharmacokinetic data exists for vancomycin in extremely low-birth-weight (ELBW) infants.
- Increasing clinical use necessitates better dosing guidelines.
Purpose of the Study:
- To develop a population pharmacokinetic model for vancomycin in ELBW infants.
- To establish an optimized vancomycin dosage regimen for ELBW infants.
- To improve vancomycin efficacy and safety in this population.
Main Methods:
- Population pharmacokinetics modeling using nonlinear mixed-effects modeling.
- Analysis of pharmacokinetic data from 19 ELBW infants.
- Model evaluation using goodness-of-fit plots, bootstrap analysis, and visual predictive checks.
Main Results:
- A one-compartment model with first-order elimination was identified.
- Body weight and serum creatinine level were significant covariates.
- An optimized dosage regimen of 5.0-7.5 mg/kg every 12 hours was determined, especially for infants with high creatinine levels.
Conclusions:
- Current vancomycin dosing recommendations may be inappropriate for ELBW infants.
- Optimized dosing is crucial for achieving therapeutic targets and minimizing toxicity.
- This study provides a basis for refined vancomycin therapy in ELBW neonates.
Abstract:
Vancomycin is a synthetic antibiotic effective against Gram-positive pathogens. Although the clinical applicability of vancomycin for infants has been increasing, the pharmacokinetic data for vancomycin in extremely low-birth-weight infants are limited. The aim of this study was to construct a population pharmacokinetics model for vancomycin in extremely-low-birth-weight infants and establish an optimal dosage regimen. We enrolled children aged less than 1 year with a birth weight of less than 1,000 g and body weight at vancomycin prescription of less than 1,500 g. Pharmacokinetic data from 19 patients were analyzed, and a population pharmacokinetics model was developed using nonlinear mixed-effects modeling software. Goodness-of-fit plots, a nonparametric bootstrap analysis, and a prediction-corrected visual predictive check were employed to evaluate the final model. The dosage regimen was optimized based on the final model. The pharmacokinetic data fit a one-compartment model with first-order elimination, and body weight and estimated serum creatinine level were used as significant covariates. In a simulation using the final model, the optimal dosage regimen, especially when the serum creatinine level (>0.6 mg/dl) was high, was 5.0 to 7.5 mg/kg of body weight twice a day every 12 h; this was required to reduce the dosage compared with that in previous studies. The recommended doses based on the current target time course concentration curves may not be appropriate for extremely-low-birth-weight infants.
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