Effect of biliary excretion on ketamine anaesthesia in the rat

Ligation of the common bile duct in rats resulted in a significant prolongation of ketamine sleeping time and a significant increase of plasma concentration of ketamine and its N-demethylated metabolite, when compared with sham-operated control animals. The treated animals also showed significant increases of plasma bilirubin and glutamate pyruvate transaminase. Cannulation of the common bile duct in rats allowed collection of samples of bile which showed high concentrations of ketamine and its N-demethylated metabolite very shortly after i.p. injection of ketamine, the amount of ketamine alone accounting for 10% of the injected dose after 2 h; including the metabolite up to 25% of the injected dose could be accounted for. In view of this we would suggest that ligation of the bile duct in rats produced a prolongation of ketamine anaesthesia by increasing plasma concentrations through interference with a major excretory route for the drug and its main metabolite.