Effect of body weight on gentamicin pharmacokinetics in neonates

Abstract

The pharmacokinetics of gentamicin in large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) newborn infants were compared in a prospective study. Serum gentamicin concentrations were drawn just before (trough) or after (peak) the third or fourth dose of gentamicin sulfate 2.5 mg/kg given as a 30-minute i.v. infusion every 12 hours to 11 LGA and 12 AGA infants. Peak (Cmax) and trough ( Cmin ) serum concentrations, elimination rate constants (k), volumes of distribution (V), and clearances (CL) were compared between the AGA and LGA groups and within the LGA group between obese (n = 6) and nonobese (n = 5) infants. The serum gentamicin concentrations achieved in the LGA infants were similar to those in the AGA infants, with Cmin values less than 2 micrograms/ml and Cmax values of 4-7 micrograms/ml. The mean pharmacokinetic variables determined were consistent with literature values reported for AGA infants. No significant differences in these variables were observed between the two groups or within the LGA group. Greater variability in Cmax, V, and CL was observed in the LGA group as a whole. The initial dose of gentamicin now recommended for AGA infants should be appropriate for LGA infants. However, serum concentrations should be monitored carefully to detect interindividual variability in pharmacokinetics so that adjustments can be made to ensure therapeutic serum concentrations.