Effects of hypoxia and azotaemia on the pharmacokinetics of amikacin in neonatal foals.

The effects of hypoxia and azotaemia on the pharmacokinetics of amikacin were evaluated in 20 full-term neonatal critically ill foals which required 24-h supportive care, antibiotics and dextrose-supplemented polyionic fluids given intravenously, nasal insufflation with oxygen and nutritional supplementation. There was no association between sepsis score or survival and pharmacokinetic parameters. Concurrent hypoxia and azotaemia were associated with significantly decreased clearance and increased peak and trough serum concentrations of amikacin; however, peaks or troughs did not exceed toxic values. Derangements in serum peak, trough and clearance values, which were present on admission, persisted over the 6-day duration of this study. Daily monitoring of serum amikacin concentration revealed a tendency to underdose (particularly in foals receiving aggressive fluid therapy), which necessitated increasing the dose/kg body weight (9-12 mg/kg) and increasing the dose interval (10-12 h) in 40% (8/20) of the cases, so that blood concentrations of amikacin could be maintained within the target range of 3-15 micrograms/ml. Amikacin-induced nephrotoxicity was not indicated by conventional laboratory testing, nor was it strongly suspected after examination of post mortem lesions.