Clinical Pharmacology of Antimicrobials in Premature Infants: Ii. Ampicillin, Methicillin, Oxacillin, Neomycin, and Colistin

The absorption, apparent volumes of distribution, serum concentrations, serum half-lives, and urinary excretion of ampicillin, methicillin, oxacillin, neomycin, and colistin were studied in premature infants by means of a micro-diffusion technique. Marked changes in serum half-lives and urinary excretion of the penicillins occurred during the first month of life. The serum half-lives of ampicillin and methicillin declined from 4.0 and 2.4 hours to 1.6 and 1.2 hours, respectively, as postnatal age increased from 1 week to 1 month. The serum half-life of oxacillin declined from 1.6 hours in 1 to 2-week-old infants to 1.2 hours in those 3 weeks of age. Concomitantly, urinary excretion rate of the penicillins increased approximately twofold as the age of infants increased from 1 week to 1 month, suggesting that immature renal function was partially responsible for the elevated serum half-lives of the penicillins in the younger premature infants. The serum half-life of neomycin was 6.5 hours in premature infants less than 2 weeks of age. It declined progressively to 3.3 hours in 3-week-old infants. The age-related changes in serum half-life were independent of birth weight. In contrast to the findings with the penicillins and neomycin, the serum half-life of colistin was not prolonged in premature infants, nor did it change with postnatal age. The mean serum half-life of colistin in premature infants was 2.4 hours. A method for using these data to calculate ampicillin, methicillin, oxacillin, neomycin, and colistin dosages appropriate for premature infants has been presented.