Population pharmacokinetics of intravenous amoxicillin in very low birth weight infants

The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (less than or equal to 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 (Va) 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: Ct (L/h) = 0.0000610 . body weight (g) and Ct (L/h) = 0.0000805 . body weight (g), for infants also receiving gentamicin and not receiving gentamicin, respectively; Vd (L) = 0.678. The interpatient standard deviation (SD) for Ct was 0.0351 Uh, 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 Ct was smaller, but the average Vd and terminal half-life (t(1/2)) were larger than previously reported for healthy adults.