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Pharmacokinetics of netilmicin in neonates

Jana Malakova, Pavla Pokorna, Zdenek Kokstein, Eva Parizkova, Vladimi’r Palic‹ka, Jiri Vortel, Josef Bukac

Med Sci Monit 1999; 5(2): CR201-207

ID: 505080

Published: 1999-03-01

Netilmicin is an important aminoglycoside antibiotic used in the treatment of most Gram-negative and some Gram-positive infections. The aim of this study was to justify initial dosage guidelines, according to Nelson and to investigate relationships between netilmicin pharmacokinetics and various neonate indices of maturation. The study group comprised 40 neonates aged between 26 to 40 weeks (gestational age). Pharmacokinetic parameters were calculated based on a one-compartment open model by means of Sawchuk and Zaskes method [1,2]. Dosage guidelines according to Nelson, [3] produced high trough netilmicin concentrations above 2 mg/l in 75% of neonates, but peak netilmicin concentrations were within the target range of 5-12 mg/l in 75% of neonates. Results demonstrate the wide interpatient variation in pharmacokinetic parameters. The mean normalized netilmicin clearance was 0.034 l/h/kg and the normalized volume of distribution was 0.506 l/kg. The increase in distribution volume and netilmicin clearance were linear with respect to the gestational and postconceptional age. The correlation between creatinine and netilmicin clearance proved to be signifficant (r=0.64, p<0.001). We recommended netilmicin dosage guidelines in neonates based upon body weight and postconceptional age, since pharmacokinetics correlate with these parameters.

Keywords: neonates, Pharmacokinetics, Netilmicin