Clinical pharmacokinetics of amikacin in hypoxic premature foals.

Abstract

The pharmacokinetics of amikacin, administered iv at 7 mg/kg, every 8 h, were evaluated over the first 48 h of hospitalisation in 7 critically ill hypoxic premature foals and compared with those in 8 full-term nonhypoxic critically ill neonatal foals. The pharmacokinetic data were used to calculate dosage schedules that would maintain the plasma amikacin concentrations in individual foals within a target range of > or = 15 micrograms/ml but < 30 micrograms/ml for peak values and < or = 3 micrograms/ml for trough values. The results indicated a statistically significant increase in the amikacin serum half-life (5.39 +/- 3.46 h) and smaller elimination rate constant (0.17 +/- 0.09 h-1) in premature foals. The pharmacokinetic derangements required increasing the dose to 8.5-10.5 mg/kg bwt in 6 of 7 premature foals and an increase in the dosage interval to 12-24 h in all 7 foals. Overall, the total dosage of amikacin was decreased in the hypoxic, premature foals so that target peaks and troughs could be maintained. Our findings suggest that prematurity and hypoxia are variables related to a prolonged serum half-life of amikacin in hypoxic, premature foals. Although there was no evidence of amikacin-induced nephrotoxicity in any of these foals, daily monitoring and tailoring of the dose schedule to the individual foal are strongly advised.