Evaluation of an empirical dosing schedule for gentamicin in neonates

The standard gentamicin dosing recommendations for neonates appear to be inappropriate because they fail to consider the influence of neonatal development on gentamicin pharmacokinetics. Recent reports have emphasized that the standard regimens of 2.5 mg/kg q8-12h produce steady-state trough serum concentrations greater than 2 micrograms/ml in up to 91 percent of preterm infants of less than 35 weeks' gestation. A new dosing schedule based on postconceptional age (PCA) was developed to provide a better guideline for initiating and maintaining gentamicin therapy in neonates: PCA greater than 34 weeks, 2.5 mg/kg iv q12h; PCA 28-34 weeks, 2.5 mg/kg iv q16h; PCA less than 28 weeks, 2.5 mg/kg iv q24h. The new dosing schedule reduced the number of neonates with elevated trough concentrations (greater than 2 micrograms/ml) from 68.4 percent to 33-40 percent. Pharmacokinetic parameters for gentamicin in the various PCA groups were determined. Volume of distribution was constant across age groups (0.5 +/- 0.09 L/kg). Elimination rate constants (kel), half-lives, and clearance rates (Cl) ranged from 0.069 +/- 0.02 to 0.14 +/- 0.04 h-1, 10.71 +/- 2.92 to 6.04 +/- 1.24 h, and 0.58 +/- 0.25 to 0.93 +/- 0.24 ml/kg/min, respectively. Significant relationships were found between kel and Cl and patient age and weight; significant correlations were found between actual and estimated (based on PCA and weight) kel and Cl. Variability in kel and Cl estimated was considerable in spite of the correlations. The observed variability stresses again the need for pharmacokinetic monitoring of gentamicin therapy in neonates.