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The effect of clinical hepatic disease on the distribution and elimination of pethidine administered post-operatively to dogs.

The pharmacokinetics of pethidine were investigated in dogs suffering from portosystemic vascular shunts and hepatic parenchymal disease. The drug was administered post-operatively at a dose rate of 2.0 mg/kg either intravenously or intramuscularly. When the drug was given intravenously to dogs suffering from intrahepatic shunts, the elimination half life was 75.5 +/- 4.2 min and the clearance rate was 29.0 +/- 2.3 ml/kg min. When the drug was given intramuscularly its rate of absorption was very slow (57.9 +/- 6.1 min) and the time taken to reach the maximum plasma concentration was long at 26.7 +/- 6.4 min. The elimination half-life for the intramuscularly administered drug was also very slow at 108.0 +/- 13 min, reflecting the reduced ability of these dogs to metabolize and eliminate pethidine. These findings suggest that caution should be exercised in the administration of pethidine to dogs suffering from hepatic dysfunction. In particular, the slower rate of absorption should be remembered in judging whether or not maximum effects have been achieved and the longer elimination half-life indicates the need to extend the intervals between repeat doses of this analgesic.