title: 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 1 >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, 4.1 +/- 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 (t1/2), 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.
authors.affiliation: Bristol Centre for Antimicrobial Research & Evaluation, Department of Medical Microbiology, Southmead Hospital, United Kingdom.
authors.forename: P E
authors.initials: PE
authors.lastname: Gosden
authors.forename: K A
authors.initials: KA
authors.lastname: Bedford
authors.forename: J J
authors.initials: JJ
authors.lastname: Dixon
authors.forename: B D
authors.initials: BD
authors.lastname: Speidel
authors.forename: A A
authors.initials: AA
authors.lastname: Leaf
authors.forename: A P
authors.initials: AP
authors.lastname: Macgowan
mesh_terms: D004334:Drug Administration Schedule; D005839:Gentamicins / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D009428:Netilmicin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D005839:Gentamicins; D009428:Netilmicin