Renal toxicity of aminoglycosides in the neonatal period

Renal toxicity of aminoglycosides seems to be less frequent in newborn infants compared to adults even though glomerular filtration rate and tubular secretion and reabsorption mechanisms are subjected to adaptive processes during the neonatal period. In 14 infants, kinetic parameters of gentamicin were determined using an open three-compartment body model. According to the lower glomerular filtration rate, the beta-elimination phase is longer in the newborn infant compared to adults, while the gamma-elimination phase is quite similar to adult values. The calculated drug accumulation in the deep compartment (kidney) under steady-state conditions is lower in newborns compared to infants. The excretion of urinary enzymes of tubular origin, that is the lysosomal NAG (N-acetyl-beta-D-glucosaminidase), beta-glucuronidase, and the brush-border-associated AAP (alanine-aminopeptidase), GGT (gamma-glutamyl-transpeptidase), are lower in healthy newborn infants compared to older ones. The increase of AAP, for instance, during aminoglycoside therapy is less pronounced in newborn infants, especially in prematures, if compared to adult values. After end of therapy the AAP excretion decreases to normal. The calculated rate of this decrease takes place in a fashion similar to the release of drugs from the kidney (gamma-elimination phase). The data indicate that there may be a lower renal accumulation of aminoglycosides in newborn infants, which can be explained by the morphometric and functional characteristics of the newborn kidney.