Biotransformation of morphine to dihydromorphinone and normorphine in the mouse, rat, rabbit, guinea pig, cat, dog, and monkey.

Biotransformation of morphine to dihydromorphinone and normorphine was studied in several mammalian species. Free and total dihydromophinone, morphine, and normorphine in the urine were determined, as propionyl derivatives, with a gas-chromatographic technique. Dihydromorphinone was detected as a morphine metabolite in the acid-hydrolyzed urine of all species studied except the dog and morphine-dependent man. Normorphine in both free and conjugated forms was detected in the urine of all species studied. The degree of biotransformation of morphine to dihydromorphinone in the guinea pig did not change during chronic administration of morphine sulfate, 25 mg/kg, daily for 28 days. The small amounts of dihydromorphinone and normorphine produced as metabolites make it unlikely that they play any significant role in the modification of the pharmacologic effects of morphine.