Influence of intrauterine maturation on the pharmacokinetics of amikacin in the neonatal period.

The effect of intrauterine maturation on amikacin disposition was studied in 29 preterm and term neonates. Mean gestational age (weeks) of the patients was 34.5 +/- 3.3 S.D. and their birth weight 1.980 +/- 920 g. After the last administration of the drug, amikacin decay was measured in plasma and urine for 100-250 h. The serum concentration versus time profiles were fitted by nonlinear regression analysis. The parameters of a 2- or 3-compartment model with elimination from the central compartment were calculated. Initial elimination T 1/2, volume of the central compartment, and steady state volume of distribution were significantly related to intrauterine maturation (respectively r = -0.76; -0.63; -0.57) whereas no significant linear correlation was found between clearance and gestational age (r = 0.19). Patients with gestational age less than 34 wk had a significantly reduced clearance when compared with the neonates with gestational age greater than 36 wk (0.78 +/- 0.17 versus 1.0 +/- 0.4 ml/h/kg, P less than 0.05). The ratio between the volumes of distribution showed that a higher amount of amikacin penetrates the peripheral compartments with increased gestational age. The renal clearance calculated in six patients averaged 66% of the total body clearance, suggesting that elimination of the drug can occur in the neonate via nonrenal routes. Analysis of the long term urinary elimination of amikacin showed that about 5% of the total amount of the drug administered in 5-8 days of treatment is retained in the organism. Although quantitatively small, this amount is relevant for the potential nephrotoxicity of the drug.