Interaction of ketamine and halothane in rats

The interaction of intramuscularly injected ketamine and its N-demethylated metabolite (metabolite I) with halothane was evaluated in rats. Five, 10, 20, or 50 mg/kg of ketamine alone or 20, 50, or 100 mg/kg of metabolite I alone produced less than 10 minutes of hypnosis. However, halothane anesthetic requirement (i.e., MAC) was depressed in a dose-dependent fashion as much as 56% 1-2 hours and as much as 14% 5-6 hours after injection of ketamine, 50 mg/kg, im. The reduction in MAC was correlated with brain levels of ketamine or metabolite I, suggesting a ketamine:metabolite I potency ration of 3:1. The half-life of ketamine in plasma and brain was longer in the presence of halothane than when ketamine was given alone. It is concluded that ketamine is not a short-acting drug and that concomitant use with halothane would be expected to prolong further the duration of its action on the central nervous system.