Umbilical versus peripheral tobramycin administration

This study evaluated the disposition of tobramycin (T) after umbilical artery catheter (UAC), intravenous (i.v.), and intramuscular administration to a group of 12 premature neonates. Patients varied in gestational age (31-42 weeks) and weight (1.76-3.98 kg). Each neonate received a 2 mg/kg dose of T at 12-h intervals for 2-15 days. Multiple blood samples after the first and last doses of T, as well as daily measurements, were made during the course of therapy. Analysis of drug concentration data revealed a biphasic distribution of T, which required a two-compartment model for description. Mean values for the alpha and beta elimination phases, t1/2 beta, Vc, and Vdss after the first dose of T were 7.604 h-1, 0.087 h-1, 11.18 h, 0.214 L/kg, and 0.645 L/kg, respectively. Average drug clearance (ClT) increased during therapy from 71 to 103 ml/min, associated with an increase in the renal function of patients. Serum concentrations of T were out of the therapeutic range in 50% of study patients. The variability of drug clearance in the neonate requires the measurement of T concentration in order to ensure safe and effective therapy.