INFLUENCE OF ENDOTOXIN-INDUCED FEVER ON THE PHARMACOKINETICS OF GENTAMICIN IN EWES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 45  (12) , 2495-2497
Abstract
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 .mu.g/kg). In the ewes with normal rectal temperature, significant (P < 0.05) increases in rectal temperature occurred before gentamicin injection and during the first 2 h. Other mild clinical signs of fever also were present. In the same ewes with endotoxin-induced fever, statistically (P < 0.05) increased gentamicin concentrations occurred at 15 and 40 min and at 6 h 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 < 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 1st 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.