Oxymorphone metabolism and urinary excretion in human, rat, guinea pig, rabbit, and dog

Oxymorphone was extensively metabolized by human, rat, dog, and guinea pig and to a lesser extent by rabbit. The most abundant metabolite in urine for all species was conjugated oxymorphone (12.7-81.7% administered dose) followed by 6 beta- and 6 alpha-carbinols produced by 6-keto reduction of oxymorphone. 6 beta-Oxymorphol (0.2-3.1%) was found in the urine of all species, whereas 6 alpha-oxymorphol (0.1-2.8%) was found only in human, rabbit, and guinea pig. Small amounts of free oxymorphone (less than or equal to 10%) were excreted by all species except rabbit, which excreted 31.7%. Overall recoveries of oxymorphone and metabolites from urine ranged from 15-96%, of which greater than 80% was excreted in the first 24 hr by all species except dog. Only 35% was excreted by dog during the first day. Stereoselectivity of 6-keto- reduction was observed for all species with the 6 beta-carbinol metabolite being most abundant in the urine of all but guinea pig. Considerable individual variability occurred in the excretion of free and conjugated oxymorphone by six human subjects following oral dosing. Species trends in the metabolism of 6-keto-opioids are discussed.