[Pharmacokinetics of netilmicin in neonates].

UNLABELLED

Our goal was to perform a pharmacokinetic analysis of netilmicin to develop the optimum dosage regimen of this antibiotic in premature neonates hospitalized in Neonate Intensive Care Unit of the Institute of Mother and Child in Warsaw.

MATERIALS AND METHODS

The pharmacokinetics of netilmicin was studied in 80 neonates, divided for analysis into three groups according to gestational age: group I - 10 full-term neonates (b.w. 3225 +/-502 g); group II - 35 premature neonates between 29-32 weeks (b.w. 1134+/-311 g); and group III - 35 premature neonates between 23-28 weeks (b.w. 910 +/-243 g). The whole studied group of neonates was initially given i.v. netilmicin every 24 h, then the dosing interval for the safety reasons was prolonged to 48 h in the premature group. The neonates received netilmicin in the following doses: group I - mean dose 6.2 +/-0.42 mg/kg; group II - 5.911+/-0.529 mg/kg and group III - 6.014+/-0.313 mg/kg. Serum netilmicin concentrations were determined by fluorescence polarization immunoassay (FPIA) - TD(x)FL(x) (Abbott).

RESULTS

The mean of pharmacokinetic parameters for groups I, II, and III were defined respectively: t(0.5) (h): 7.14+/-1.88, 12.68+/-4.26, 15.98+/-5.9; AUC0-( (microg x h/ml): 149+/-41, 303+/-100, 401+/-172; Cl/kg (l/h/kg): 0.748+/-0.24, 0.371+/-0.13, 0.289+/-0.1; MRT0-( (h): 6.3+/-2.8, 10.8+/-6.3, 15.5+/-9.3; V(dss) (l/kg): 0.75+/-0.24, 0.59+/-0.52, 0.44+/-0.19. The obtained mean netilmicin serum concentrations (microg/ml) were: once-a-day dosage: C(max) - 10.25+/-2.616 (group I), 12.2+/-2.65 (group II), 12.9+/-2.77 (group III); C(min) - 1.158+/-0.657 (group I), - 2.65+/-1.02 (group II), 3.23+/-1.42 (group III); once-a-48 h dosage: C(max) - 11.7+/-1.09 (group II), 13.9+/-6.53 (group III); C(min) - 1.09+/-0.64 (group II), 1.74+/-0.98 (group III).

CONCLUSIONS

1. All the calculated pharmacokinetic parameters in the premature neonate groups (group II and III) significantly differs from the parameters calculated for full-term neonates. 2. Significant correlations were obtained between birth weight, gestational age and all the calculated pharmacokinetic parameters in all the groups of neonates. 3. The obtained results indicated that the use of the dosing schedule of netilmicin with the dose intervals of 48 h in premature neonates should guarantee adequate peak and trough levels without the need of routine monitoring of each patient in the premature neonate group except the very low weight neonates. Detection of the specific sensitivity of lymphocytes T during the diagnosis of food allergy.