PEDIATRICS Vol. 39 No. 1 January 1967, pp. 97-107
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CLINICAL PHARMACOLOGY OF ANTIMICROBIALS IN PREMATURE INFANTS: II. AMPICILLIN, METHICILLIN, OXACILLIN, NEOMYCIN, AND COLISTIN

Stanton G. Axline M.D.1, Sumner J. Yaffe M.D.1, and Harold J. Simon M.D., Ph.D.1

1 The Division of Infectious Diseases, Department of Medicine, Stanford University School of Medicine. Palo Alto, California, and the Department of Pediatrics, State University of New York School of Medicine, Buffalo, New York

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.

Submitted on April 4, 1966
Accepted on August 4, 1966




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