Effect of gestational age and birth weight on tobramycin kinetics in newborn infants

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Abstract
The effects of gestational age and birth weight on tobramycin kinetics were studied in 26 newborn infants with presumed or proven bacterial sepsis during the first week of postnatal age. The infants received tobramycin, 2·5 mg/kg intravenously every 12 h. Group A consisted of nine patients 28 to 30 weeks of gestational age; group B had 11 patients >30 to ≤34 weeks of gestational age; and group C had six patients >34 to ≤40 weeks of gestational age. Steady-state peak serum concentrations of tobramycin averaged 6·5, 7·2 and 7·1 mg/l in groups A, B and C; the corresponding trough concentration averaged 2·0, 2·3 and 1·3 mg/l. The frequency of tobramycin trough serum concentration above 2 mg/l was 44% in group A, 45% in group B and 0% in group C. Total body clearance of tobramycin averaged 1·04, 1·13 and 1·28 ml/min/kg; apparent volume of distribution averaged 0·84, 0·81 and 0·61 1/kg; and elimination half-life averaged 9·3, 8·9 and 5·6 h in groups A, B and C. Group M consisted of seven infants with 1·0–1·25 kg birth weight; group N had six infants 1·26–1·50 kg birth weight; group O had seven infants 1·51–2·0 kg birth weight; and group P had six infants 2·1–3·5 kg birth weight. Steady-state peak serum concentration of tobramycin averaged 5·7, 7·3, 7·8 and 7·1 mg/l; and the trough serum concentration averaged 2·2, 2·4, 1·9 and 1·3 mg/l in groups M, N, O and P. The frequency of tobramycin trough serum concentration exceeding 2 mg/l was 43% in group M, 50% in group N, 43% in group O and 0% in group P. Total body clearance of tobramycin averaged 1·05, 1·12, 1·10 and 1·28 ml/min/kg; apparent volume of distribution averaged 1·02, 0·74, 0·69 and 0·61 1/kg; and elimination half-life averaged 11·3, 8·2, 7·5 and 5·6 h in groups M, N, O and P. These data indicate that infants < 34 weeks gestational age, particularly those < 1·5 kg birth weight, may require a longer dosing interval than currently recommended.