Tobramycin sulfate elimination in premature infants

The elimination pharmacokinetics of tobramycin sulfate was studied in 25 newborn infants of birth weight 0.7 to 4.7 kg during 31 treatment episodes. The peak serum concentrations after a 2.5 mg/kg dose were usually within the therapeutic range of 5 to 10 micrograms/ml; however, the serum predose trough values were elevated above the theoretical safe limit of 2 micrograms/ml. Because of the prolonged serum elimination half-lives, a calculated extended dosage interval, sometimes greater than 24 hours, was necessary to obtain a predose trough of less than or equal to 2 micrograms/ml. The serum elimination half-lives inversely correlated with gestational age, extrauterine age, birth weight, and creatinine clearance. The very low ratio of tobramycin renal clearance to creatinine renal clearance was virtually constant and indicated a probable tubular reabsorption of tobramycin. A general dosage schedule based on birth weight was derived from the data. An alternative formula was derived to enable prediction of the tobramycin elimination half-life based on a combination of birth weight, gestational age, and extrauterine age for an infant younger than 7 days of age.