May 23rd, 2011 | Add a Comment
Ketamine is metabolized extensively by hepatic microsornal enzymes. Ketamine metabolism is demethylated to the corresponding N-desmethyl compound to form norketamine (about 60%) the main metabolite.
Norketamine rapidly appears (approximately within 5 minutes) in plasma following ketamine administration and had a terminal half-life of 63.6 +1- 23.9 minutes.
In animals, norketamine is one-fifth to one-third as potent as ketamine. This active Ketamine metabolism may contribute to prolonged effects of ketamine.
The other important metabolite is dehydronorketamine formed after the hydroxylation of norketamine. Chronic administration of ketamine metabolism stimulates the activity of enzymes responsible for its metabolism and drug tolerance.
Accelerated metabolism of ketamine as a result of enzyme induction could explain, in part, the observation of tolerance to the analgesic effects of ketamine that occurs in patients receiving repeated doses of this drug.
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