Antipyretic and pharmacokinetic evaluation of coumarin in the rabbit after endotoxin administration

The antipyretic effect of coumarin (C) and the drug disposition of C and its metabolites, 7-hydroxycoumarin, 7-HOC, and 7-hydroxycoumarin glucuronide, 7-HOCG, upon endotoxin challenge were studied in an animal model. A parallel design was used with 6 rabbits each in the following groups: control, coumarin 1 mg/kg I.V., endotoxin 0.125 mg/kg I.V., and coumarin 1 mg/kg I.V. plus endotoxin 0.125 mg/kg I.V. C reduces the elevated temperature significantly during the first half hour with the mean temperature difference versus time curve being lower than that for the endotoxin challenged group. Although not significant there is a trend for increased elimination half-life and apparent volume of distribution for C. The apparent volume of distribution for 7-HOC and 7-HOCG increased significantly, and the elimination half-life of 7-HOCG increased significantly.