THE DISTRIBUTION AND FATE OF MORPHINE IN THE NON-TOLERANT AND TOLERANT MONKEY

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

The subcutaneous administration of 30 mgm./kgm. of morphine in nontolerant monkeys results in the prompt appearance of free and bound morphine in the plasma, the maximum levels of bound morphine being three to four times those observed for free morphine. The biologic half-life for free morphine is about three and one-half to four hours and for bound morphine four to six hours.

A comparison of the urinary and fecal excretion of morphine in the non-tolerant and tolerant monkeys shows trends toward a decrease in urinary excretion and an increase in fecal excretion in the tolerant animals. However, there is no statistical difference between the two groups of animals. Only about 75 per cent of the administered morphine can be accounted for in monkeys which is a much lower fraction than that found with the dog. Accordingly, the monkey must possess a mechanism of detoxication other than conjugation and elimination. Fecal excretion in the monkey was shown to be a much less important factor than in the dog.

The distribution of free and bound morphine in monkeys is selective for certain tissues and fluids. Bound morphine is found in gall bladder bile in concentrations many times greater than those observed in tissues and other fluids. Brain, spinal cord, and cerebrospinal fluid contain very little morphine in either the free or the bound form.