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Population pharmacokinetics of intravenous amoxicillin in very low birth weight infants
B G Charles1, Y Preechagoon, T C Lee
1School of Pharmacy, University of Queensland, St. Lucia, Australia.
Insights
Population pharmacokinetics of amoxicillin in very premature infants show lower clearance and higher volume of distribution compared to adults. This study provides a model for optimizing amoxicillin dosing in this vulnerable population.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Clinical Pharmacy
Background:
- Premature infants have unique physiological characteristics affecting drug pharmacokinetics.
- Optimizing antibiotic dosing is crucial for effective treatment and minimizing toxicity in neonates.
Purpose of the Study:
- To characterize the population pharmacokinetics of intravenous amoxicillin in very premature infants.
- To develop a pharmacokinetic model to guide amoxicillin dosing in this population.
Main Methods:
- Population pharmacokinetic analysis using a one-compartment model with first-order elimination.
- Serum amoxicillin concentrations measured by High-Performance Liquid Chromatography (HPLC).
- Covariate analysis including body weight and concomitant gentamicin use.
Main Results:
- Developed population pharmacokinetic models for amoxicillin clearance (CL) based on body weight.
- Found amoxicillin CL was lower and volume of distribution (Vd) was larger in infants compared to adults.
- Model demonstrated good predictive performance with insignificant bias in a validation group.
Conclusions:
- The developed population pharmacokinetic model accurately describes amoxicillin disposition in very premature infants.
- Findings suggest amoxicillin dosing may need adjustment in premature neonates compared to adult recommendations.
- This model can aid in individualizing amoxicillin therapy for improved outcomes in very premature infants.
Abstract:
The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (< or = 32 week gestational age, < 1500 g birth weight) who were receiving intravenous amoxicillin (50 mg/ kg, every 12 h) during the first days after birth. Serum amoxicillin concentrations were measured by HPLC. Clearance (CL) and volume of distribution (Vd) were modeled alone and under the influence of demographic and clinical covariates with a 1-compartment model with first-order elimination. The final population models with influential covariates were: CL(L/h) = 0.0000610 x body weight (g) and CL (L/h) = 0.0000805 x body weight (g), for infants also receiving gentamicin and not receiving gentamicin, respectively; Vd(L) = 0.678. The interpatient standard deviation (SD) for CL was 0.0351 L/h, and for Vd was 0.365 L. The intrapatient variability (SD) among observed and model-predicted serum concentrations was 13.7 mg/L. Evaluation of the predictive performance of this model in another group of infants (n = 16) indicated statistically insignificant bias (p > 0.05) of 3 mg/L among pairs of observed and Bayesian-predicted amoxicillin concentrations. The average population CL was smaller, but the average Vd and terminal half-life (t1/2) were larger than previously reported for healthy adults.