Influence of endotoxin-induced fever on the pharmacokinetics of gentamicin in ewes.

The pharmacokinetics of gentamicin (3 mg/kg of body weight) were evaluated in 6 adult ewes before and after fever was induced with Escherichia coli endotoxin (1 micrograms/kg). In the ewes with normal rectal temperature, significant (P less than 0.05) increases in rectal temperature occurred before gentamicin injection and during the first 2 hours. Other mild clinical signs of fever also were present. In the same ewes with endotoxin-induced fever, statistically (P less than 0.05) increased gentamicin concentrations occurred at 15 and 40 minutes and at 6 hours after injection of gentamicin. Changes were not observed in the apparent volume of distribution calculated by the area method, the volume of distribution at steady state, the overall biological half-life, or body clearance. Significant (P less than 0.05) reductions occurred in the zero time intercept for distribution, the distribution rate constant, the concentration in plasma at time of injection, the volume of the peripheral compartment, and the first order transfer rate constants; only the volume of the central compartment was increased. Total amounts of gentamicin were increased in the central compartment and decreased in the peripheral or tissue compartment.