[Optimalisation of netilmicin dosage based on therapeutic drug monitoring during the first days of life in very preterm neonates (gestational age 23-32 weeks)]. / Optymalizacja dawkowania netylmycyny w oparciu o terapie monitorowana stezeniem antybiotyku w pierwszych dniach zycia u noworodków bardzo niedojrzalych (23-32 tygodnie ciazy).

AIM: The aim of this study was to optimalise netilmicin dosage in low and very low birthweight premature neonates, based on drug serum concentrations obtained during therapeutic drug monitoring (TDM). PATIENTS AND METHODS: Prospective study of 55 neonates born at gestational age 23-32 (GA) and birthweight between 480 g to 1780 g, with suspected intrauterine infection, in whom netilmicin serum concentration was monitored. Initially the antibiotic was administered every 24 hours (group I: n=16; mean GA=28+/-3 weeks). Peak level was measured 30 minutes after completion of infusion after the 2(nd) dose of the drug, and trough level was measured immediately before administration of the 3(rd) dose of the drug. Due to excessive trough levels, the dosing regimen was modified, prolonging the interval between doses to 48 hours. Such dosing regimen was used in neonates, enrolled in group II (n=39; mean GA=28+/-2 weeks). Pharmacokinetic parameters were evaluated in order to find correlations between them and neonatal maturity, birthweight and creatinine serum concentration. Serum netilmicin concentration was measured by fluorescence polarization immunoassay (FPIA), using TDx/FLx (Abbott Laboratories). Creatinine concentration was measured on the 3(rd) day of life using Cobas Integra 400. All children in the study underwent the first hearing examinations under 3 months of age. After excluding changes which could affect hearing ability, behavioural examination was conducted. If its result was inconclusive or abnormal, the child was referred for ABR (auditory brain stem response) examination. The children were followed-up until they were 2 years old. RESULTS: Netilmicin peak levels in both groups were within the recommended range (11.33+/-3.27 microg/mL in group I; 13.35+/-5.67 microg/mL in group II). Safe trough level was exceeded in 81.2% neonates in group I and 28.2% in group II. This was observed in the most immature neonates: born 23-27(th) GA, with mean birthweight 805+/-293 g, in whom trough level was on average 2.93 microg/mL and t(0.5) was 20.8 hours. Negative correlation was found between trough level and gestational age (r=-0.524; p<0.001) and birthweight (r= -0.293; p=0.030). Negative correlations was also found between t(0.5) and gestational age (r= -0.489; p<0.001) and birthweight (r=-0.320; p=0.016). No child was diagnosed with hearing impairment in group II and one case in group I. CONCLUSIONS: The results indicate that netilmicin dosage of 6 mg/kg every 48 h can ensure the desired trough and peak levels in premature neonates without the necessity of routine monitoring of antibiotic concentration. However, in very premature neonates (

[Pharmacokinetics of netilmicin in neonates]. / Farmakokinetyka nietylmycyny u noworodków przedwczesnie urodzonych.

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.