Tobramycin pharmacokinetics in very low birth weight infants.

Tobramycin is commonly used at a dose of 2.5 mg kg-1 12h-1, but this regimen often results in trough serum concentrations exceeding 2 mg l-1. Because of limited data in infants weighing less than 1,000 g at birth, we studied eight newborn infants (gestational age 24-30 weeks; postnatal age 3 X 4 days; birth weight 0.60-0.97 kg) at a modified dosing regimen of 2.5 mg kg-1 18 h-1 or 3.0 mg kg-1 24 h-1. Tobramycin peak and trough serum concentrations ranged from 6.0-10.8 (7.8 +/- 1.5) mg l-1 and 1.2-2.4 (1.7 +/- 0.4) mg l-1, respectively. Serum concentration exceeded 2 mg l-1 in seven of eight patients at 12 h and two of eight at 18 h; none had a trough serum concentration above 2 mg l-1 at 24 h. Total body clearance ranged from 0.55 to 0.82 (0.69 +/- 0.10) ml min-1 kg-1; apparent volume of distribution ranged from 0.44 to 0.71 (0.59 +/- 0.10) 1 kg-1; and elimination half-life ranged from 7.7 to 12.6 (9.9 +/- 1.5) h. These data indicate that the modified dosage regimen of 2.5 mg kg-1 18 h-1 or 3.0 mg kg-1 24 h-1 appears to be more acceptable than the current regimen in achieving effective and safe peak and trough serum concentration of tobramycin in newborn infants weighing less than 1 kg at birth.