THE NEED FOR A LOADING DOSE OF GENTAMICIN (G) IN NEONATES

Abstract

G often has a prolonged half life (T½) in premature or sick newborns; therefore, modified G dosing schedules have been developed, with longer dosing intervals to accommodate increased T½. Neonates also have wide variability in distribution volumes (Vd). In adults, early attainment of therapeutic levels of aminoglycosides has been correlated with positive outcome from gram negative sepsis. Neonates with large Vds may not achieve therapeutic peaks (5-10ug/ml) in the first 48° of therapy.

We studied 100 consecutive patients. G levels were drawn 1½°, 4° and 8° after a dose. Pharmacokinetic variables were calculated with a one-compartment open model. Results are mean±SD (GA=gestational age, BW=birthweight, Cl=clearance, PN=postnatal age).

In this population, 2.5mgkg of G would result in an initial peak level of <5ug/ml in 45% of the patients. A loading dose of 4mg/kg would result in a peak of ≥5ug/ml in 92% of the patients and a peak of >12ug/ml in 7%. G toxicity appears to be related to high levels over time, whereas therapeutic efficacy may be related to adequate initial levels. We therefore recommend an initial G loading dose of 4mg/kg in newborns.

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