SUMMARY 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 (O 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 (>2 mg/l) were recorded in 57 of 91 (63%) neonates; 24 of these had trough concentrations greater than 3 mg/I. 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.Gentamicin is a valuable broad spectrum antibiotic and is extensively used for the treatment of serious sepsis in the newborn. It is ototoxic and nephrotoxic in the adult,1-3 and although toxicity in the neonate is not well documented, it would be reasonable to expect similar or more pronounced effects to those seen in adults. To avoid toxic effects it has been suggested that trough serum gentamicin concentrations should be below 2 mg/l and that peak values should not exceed 12 mg/1.4 5 Peak serum values less than 4 mg/l are considered subtherapeutic.6 Using these criteria, the incidence of putatively toxic and of subtherapeutic serum concentrations of gentamicin were determined in a study of the records of 64 neonates: a further 27 neonates were examined prospectively. Data on physiological and clinical factors that influence serum values and total body clearance of gentamicin were analysed. Materials and methodsStudy population. Ninety one neonates (52 boys and 39 girls) between 1 and 28 days of age were treated. Fifty one of 91 babies began treatment in week 1 of life. Their gestational age and birthweight were mean (SEM) 31 (0-5) weeks (range 25-40 weeks) and 1725 (100) g (range 700-4300 g) respectively. The dose of gentamicin was mean (SD) 5 5 (0. 1) mg/kg/day divided 12 hourly and administered by either the intravenous or intramuscular route.Specimen collection and assay of gentamicin. One hundred and thirty eight blood samples (300 ,ul) were collected by heelprick immediately before (trough value) and one hour after (peak value) gentamicin. One hundred and thirty of 138 specimens were collected more than 48 hours after treatment began, that is at 'steady state'. Gentamicin concentration was determined on the day of recei...
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