The influence of endotoxin-induced pyrexia on the pharmacokinetics of gentamicin in the rabbit

Endotoxin-induced pyrexia caused a 2-fold increase in the volume of distribution of intravenously administered gentamicin in the rabbit as compared to the basal state (0.13-0.23 and 0.31-0.65 l for the central and peripheral compartments, respectively). Elimination, half-life was prolonged (46 to 90 min control and pyrexia, respectively), total plasma clearance remaining unchanged (4.6 and 4.9 ml/min, respectively). Endotoxin-induced pyrexia caused a significant increase in the serum concentrations and area under the concentration-time curve of gentamicin administered intramuscularly (355 to 704 microgram . min/ml, control and pyrexia, respectively). The increase in gentamicin concentration area under the curve was positively correlated with the temperature load (P less than .01). As total plasma clearance was not affected by pyrexia, the increased serum concentrations after intramuscular injection may be explained by enhanced absorption from the site of administration.