Studies on the distribution and metabolism of ketamine in sheep

A comparison of the distribution and metabolism of intravenous and intra-cerebroventricular ketamine hydrochloride in sheep showed that following intravenous administration there was a rapid biexponential decline in plasma ketamine, metabolism was rapid and both the demethylation and subsequent oxidation metabolites were detected. In the urine the second metabolite appeared to be the major one together with a third unidentified metabolite. In the CSF both ketamine and the first metabolite appeared to follow the plasma concentrations, but the entry of the second metabolite seemed to show a much slower pattern. Following injection of ketamine into the lateral cerebral ventricles the levels of ketamine in the CSF declined rapidly and the plasma concentration of ketamine showed a similar pattern to that seen following intravenous injection, indicating a rapid transfer to the blood. The levels of the metabolites found in the CSF suggest that their production does not take place in the CSF and that they penetrate back from the plasma. The findings of rapid metabolism following both routes of injection suggests that metabolism plays a major part in the termination of the effects of ketamine in the sheep, and that plasma levels of ketamine are of more importance than CSF levels in the maintenance of anaesthesia.