Population Pharmacokinetics and Dosing Optimization of Amoxicillin in Chinese Infants.

ABSTRACT

Amoxicillin is used to treat various bacterial infections (eg, pneumonia, sepsis, meningitis) in infants. Despite its frequent use, there is a lack of population pharmacokinetic studies in infants, resulting in a substantial variability in dosing regimens used in clinical practice. Therefore, the objective of this study was to evaluate the population pharmacokinetics of intravenous amoxicillin in infants and suggest an optimal dosage regimen. Blood samples were collected for the determination of amoxicillin concentrations using an opportunistic sampling strategy. The amoxicillin plasma concentrations were determined using high-performance liquid chromatography. Population pharmacokinetic analysis was performed using NONMEM. A total of 62 pharmacokinetic samples from 47 infants (age range, 0.09 to 2.0 years) were available for analysis. A 2-compartment model with first-order elimination was most suitable to describe the population pharmacokinetics of amoxicillin, and covariate analysis showed that only current body weight was a significant covariate. Monte Carlo simulation demonstrated that the currently used dosage regimen (25 mg/kg twice daily) resulted in only 22.4% of infants reaching their pharmacodynamic target, using a minimum inhibitory concentration (MIC) break point of 2 mg/L, whereas a dosage regimen (60 mg/kg thrice daily), as supported by the British National Formulary for Children, resulted in 80.9% of infants achieving their pharmacodynamic target. It is recommended to change antibiotics for infections caused by Escherichia coli (MIC = 8.0 mg/L) because only 27.9% of infants reached target using 60 mg/kg thrice daily.