Hydromorphone undergoes biotransformation at the 3- and 6-positions in the liver. Involvement of the cytochrome P450 system in the metabolism of hydromorphone has not been established. At the 3-position, hydromorphone forms a glucuronide ether via UDP-glucuronyl transferase; greater than 95% of the dose is metabolized to hydromorphone-3-glucuronide. At the 6-position, hydromorphone is reduced to form dihydromorphone and dihydroisomorphone via NADPH dihydromorphinone ketone reductase. Dihydromorphone and dihydroisomorphone have been shown to be active in animal models but not in humans. The pharmacologic activity of the 3-glucuronide metabolite has not been established; although, in rat studies, this compound caused excitatory behavior including myoclonus, ataxia, and tonic-clonic seizures similar to the 3-glucuronide metabolites of morphine.[25632] In high doses, hydromorphone has been reported to cause excitation. Hydromorphone metabolites are primarily excreted in the urine; only a small amount of the hydromorphone dose is excreted unchanged in the urine. The glucuronide conjugate is also excreted in bile, but enterohepatic circulation is a minor excretion pathway. The half-life of immediate-release hydromorphone is 2—3 hours with a duration of analgesia of 3—4 hours. The mean half-life of extended-release hydromorphone tablets (Exalgo) is 11 hours.
ya, stupid doctors :eyeroll