Incidence of potentially toxic concentrations of gentamicin in the neonate

The incidence of putatively toxic serum concentrations and the factors influencing their occurrence were investigated in a study of 91 neonates receiving parenteral gentamicin twice daily at a dose of mean (SD) 5.5 (0.1) mg/kg/day. Most neonates were preterm and of low birthweight. Serum concentrations, area under the curve (AUC), and clearance were calculated. Potentially toxic trough concentrations (greater than 2 mg/l) were recorded in 57 of 91 (63%) neonates; 24 of these had trough concentrations greater than 3 mg/l. These babies were of a significantly lower gestational age and were younger than the remainder of the population. Toxic trough concentrations were not accompanied by raised peak serum values. A wide variation in all pharmacokinetic variables was observed. Peak serum concentration was most highly correlated with dose, while trough concentration, AUC, and clearance were more dependent on postnatal age. Clearance of gentamicin decreased significantly with increasing serum urea and creatinine concentrations. Preterm neonates in the first week of life are likely to develop potentially toxic serum concentrations when receiving the currently recommended dose of gentamicin (5-6 mg/kg/day). To prevent accumulation the dosage interval may need to be increased to 18 hours in these babies.