Pharmacologic studies in neonates given large dosages of ampicillin

The clinical pharmacology of ampicillin in neonates was studied. Ampicillin was effective in vitro against the common gram-pesitive pathogens and most E. coli causing neonatal bacterial diseases. Synergy was demonstrated in vitro for 40 per cent of E. coli using combinations of ampicillin and gentamicin. The pharmacokinetic properties of ampicillin in premature and full-term infants given 50, 75, or 100 mg. per kilogram per dose intramuscularly were investigated. Mean peak serum ampicillin values in premature infants 1 to 3 days of age were 104, 166, and 204 μg per milliter after 50, 75, and 100 mg. per kilogram per dose, respectively. There was no significant drug accumulation in serum and, half-life values were related inversely to postnatal age. Ampicillin levels in cerebrospinal fluid of 1 to 28 μg per milliliter after 40 to 70 mg. per kilogram per dose were 11 to 65 per cent, respectively, of the simultaneous serum values. Dosage recommendations are presented.