The Need for a Loading Dose of Gentamicin in Neonates

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Abstract
We studied pharmacokinetic variables in 100 neonates to evaluate the need for a loading dose of gentamicin. The mean volume of distribution for gentamicin in this population was .542 .+-. .205 L/kg. Forty-five percent of these patients would not achieve peak seurm concentrations of .gtoreq.5 .mu.g/ml after one dose of 2.5 mg/kg. A loading dose of 4 mg/kg would result in a level of .gtoreq.5 .mu.g/ml in 92% of the patients. After this study, a 4 mg/kg loading dose was initiated at our institution. Peak and trough concentrations at steady state were compared in 50 patients receiving a loading dose and 40 patients who had not received a loading dose. No significant differences were found in peak or trough concentrations after three or more doses, verifying that a loading dose does not affect steady-state concentrations. Because gentamicin toxicities are related to accumulation over time, whereas therapeutic efficacy may be related to early attainment of therapeutic peak serum concentrations,we recommended a loading dose of 4 mg/kg in all neonates beginning gentamicin therapy.

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