Intrapatient variation in tobramycin kinetics in low birth weight infants during first postnatal week

Nineteen newborn infants receiving tobramycin, 2.5 mg/kg every 12 h were studied on two occasions at steady-state during the first week of postnatal age. The two studies were separated by two to four days. Total body clearance of tobramycin averaged 1.15 and 1.14 ml/min/kg (p greater than 0.05), apparent volume of distribution averaged 0.82 and 0.68 l/kg (p greater than 0.05), and elimination half-life averaged 8.6 and 7.1 h (p greater than 0.05), during the first and second study, respectively. When the data were further analyzed based on the birth weight, tobramycin kinetics changed during the second study compared to the first study in very low birth weight infants. In eight infants less than or equal to 1.5 kg birth weight, although total clearance of tobramycin was similar, the average apparent volume of distribution decreased from 1.04 l/kg during the first study to 0.73 l/kg during the second study (p less than 0.05) and elimination half-life from 11.1 h during the first study to 8.7 h during the second study (p less than 0.05). These data indicate that these infants may require a change in dosing interval with continued tobramycin therapy during the first week of postnatal age. Intrapatient variation in tobramycin kinetics should be considered, in addition to the interpatient variation reported previously, when monitoring the serum concentration to individualize tobramycin therapy in newborn infants less than or equal to 1.5 kg birth weight.