Pharmacokinetics of Once-a-Day Netilmicin (4.5 mg/kg) in Neonates

Abstract

The pharmacokinetics of once-a-day netilmicin (4.5 mg/kg) was studied in 16 neonates, divided for analysis into three groups according to gestational age: group I >36 weeks (n=7); group II between 34-36 weeks (n=4); and group III <34 weeks (n=5). The serum netilmicin (mean ± SD) 4h and 24h after the first dose were 4.7 ± 0.8 and 0.8 ± 0.5 mg/L; 4.9 ± 0.8 and 1.9 ± 0.2 mg/L; 4.9 ± 0.5 and 1.7 ± 0.5 mg/L in groups I, II and III respectively. After the second dose, concentrations at 2, 4, 8, 16 and 24 h were 7.2 ± 1.0, 5.0 ± 0.8, 3.0 ± 0.6, 1.7 ± 0.4 and 0.9 ± 0.2 mg/L (group I); 8.6 ± 0.2, 6.1 ± 0.5, 4.2 ± 0.7, 2.6 ± 0.1 and 1.4 ± 0.4 mg (group II); 9.0 ± 1.2, 6.3 ± 0.9, 4.0 ± 0.7, 2.6 ± 0.5 and 1.7 ± 0.3 mg/L (group III). There was a large degree of inter-patient variability in serum concentrations and serum half-life (t½), volume of distribution (VD), area-under-the-curve (AUC), relative serum clearance (Clp) such that these parameters could not be correlated to age or weight. Absolute serum clearance (L/h) was correlated with gestational age (r = 0.672, P <0.01). There was no statistically significant evidence of accumulation between the first and second doses for any patient group. One baby from each group II and group III had concentration >2 mg/L 24h after the first dose and one baby from group III had concentration >2 mg/L 24h after the second dose. There are no established correlations between serum netilmicin concentrations and efficacy or toxicity in neonates and keeping 24 h trough concentration below 2 mg/L with a once-a-day dose of 4.5 mg/L would have to be validated in terms of its clinical efficacy and potential toxicity in a neonatal population.