Pharmacokinetics of a netilmicin loading dose on the first postnatal day in preterm neonates with very low gestational age.
OBJECTIVE
Pharmacokinetic parameters are important for dose adjustment of aminoglycosides, but they are highly variable in neonates. In this study the pharmacokinetics of a netilmicin loading dose was investigated on the first postnatal day in preterm neonates with very low gestational age (GA).


METHODS
In an open prospective study, 20 neonates with GA between 22.9 and 32.0 weeks and suspected postnatal bacterial infection received an intravenous loading dose of 5 mg/kg netilmicin over 1 h during the first postnatal day. Netilmicin serum concentrations were determined by an enzyme multiplied immunoassay.


RESULTS
The systemic clearance of netilmicin normalized to body weight (BW) was not significantly different in three GA subgroups (0.59+/- 0.02 ml/min/kg for GA <24 weeks, 0.72+/-0.14 ml/min/kg for GA 24-27 weeks, and 0.62+/-0.19 ml/min/kg for GA 27-32 weeks, P=0.123). Similar results were also obtained for serum elimination half-time and for the distribution volume normalized to BW. Multiple regression analysis showed that systemic clearance and volume of distribution (both not normalized to BW) significantly correlated with BW (P<0.0001) but not with GA. In the entire group, 20% of peak concentrations were below the target of 6 mg/l, and 63% of trough concentrations were above the target of 2 mg/l.


CONCLUSIONS
In neonates with very low GA, the pharmacokinetic parameters of netilmicin determined after an intravenous loading dose were not dependent on GA when normalized to BW. A number of neonates did not reach targeted peak and trough netilmicin serum concentrations, suggesting that a higher loading dose and a prolonged dosing interval might enhance the effectiveness and safety of netilmicin in preterm neonates immediately after birth.
Rengelshausen
Jens
J
Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Beedgen
Bernd
B
Tsamouranis
Konstantina
K
Mikus
Gerd
G
Walter-Sack
Ingeborg
I
Haefeli
Walter E
WE
Linderkamp
Otwin
O
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001724:Birth Weight; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D009428:Netilmicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies
D000900:Anti-Bacterial Agents; D009428:Netilmicin