391 GENTAMICIN THERAPY IN PREMATURE NEONATES: DOSAGE INTERVAL (DI) BASED ON GESTATIONAL AGE (GA)

Abstract

Peak gentamicin serum concentrations (GSC) of 4-12 mcg/ml and trough concentrations < 2 mcg/ml are recommended for effective therapy without toxicity. Currently recommended gentamicin dosage regimens for premature neonates within the first week of life have a significant incidence of toxic or subtherapeutic GSC. In a previous study by the authors using a standard regimen with fixed DI, an inverse linear correlation was found between peak and trough GSC and GA. A new gentamicin dosage regimen was formulated based on this correlation using a one-compartment pharmacokinetic model. This regimen consists of a 3.5 mg/kg dose given at a DI which is inversely related to GA: DI = 50.5 - 0.76 GA. This regimen is designed to yield peak and trough GSC of 8.0 mcg/ml and 1.5 mcg/ml, respectively, in premature infants, irrespective of GA. To test this new regimen, 32 premature neonates were studied within the first week of life. Mean GA was 31.4 weeks (range 25-36); mean birth weight was 1675 grams (range 570-2900). Mean peak and trough GSC (± SD) were 7.0 ± 1.17 mcg/ml and 1.1 ± 0.26 mcg/ml, respectively. All GSC were within the recommended range. This is the lowest incidence of inappropriate GSC in any series reported in the literature. Serial peak and trough GSC did not vary significantly in individual patients during the first 4 days of therapy. The previously observed correlation between GSC and GA was lost with this regimen. We conclude that relating DI to GA in this fashion is a simple and effective way of achieving optimal peak and trough GSC in premature infants of various GAs.