Metabolism

Ketamine is metabolized by hepatic microsomal enzymes. The major pathway involves N-demethylation to form norketamine (metabolite I), which is then hydroxylated to hydroxynorketamine. These products are conjugated to water-soluble glucuronide derivatives and are excreted in urine.^{[285] [444] [446]} The activity of the principal metabolites of ketamine has not been well studied, but norketamine has been shown to have significantly less (between 20% and 30%) activity than the parent compound.^{[447] [448] [449]} Little is known about the activity of the other metabolites, but it is probable that ketamine is the major active drug.