DISTRIBUTION AND FATE OF NALORPHINE IN THE DOG AND RAT

¹ Department of Pharmacology, University of Michigan Medical School, Ann Arbor

Following the subcutaneous administration of 30 mgm./kgm. of nalorphine to dogs, the biologic half-life of the free drug in plasma is about one and one-half to two hours and that of conjugated nalorphine about two and one-half hours. In the same animal species the urinary recovery of the administered dose of drug is one to four per cent as free nalorphine, 42 to 56 per cent as conjugated nalorphine, and 44 to 60 per cent as total nalorphine. Essentially all of the free nalorphine appears in the urine three to four hours after injection. Very little total nalorphine is found in the urine after twenty-four hours. Nalorphine is conjugated more quickly and more completely by the dog than morphine.

The concentrations of free and conjugated nalorphine in most tissues and fluids of dogs and rats are lower than those described for morphine. Compared with other tissues, the concentration of conjugated nalorphine in gall bladder bile is very high but still accounts for no more than a few per cent of the administered drug.

In rats the rate of absorption of nalorphine following subcutaneous injection is more rapid than that of morphine.