Interaction of ketamine and halothane in rats

Abstract

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 min of hypnosis. However, halothane anesthetic requirement (minimum alveolar concentration) was depressed in a dose dependent fashion as much as 56% 1-2 hr and as much as 14% 5-6 hr 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 ratio 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.