THE SYNTHESIS AND ESTIMATION OF N-C¹⁴-METHYL LABELED LEVORPHANOL AND ITS BIOLOGICAL DISPOSITION IN THE MONKEY, DOG AND RAT

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

The synthesis of N-C¹⁴-methyl labeled levorphanol is reported. A method is described for the estimation of N-C¹⁴-methyl labeled levorphanol in biological material which is sensitive to a level of 2.5 millimicrogm./ml. of plasma or urine (if 2-ml. samples are analyzed) when the drug has a specific activity of about 1 millicurie/mM. The procedure has been shown to be specific for levorphanol and to give adequate recoveries.

Plasma levels of free and conjugated levorphanol have been obtained for the dog and monkey after the subcutaneous injection of 0.2 and 2.0 mgm./kgm. of drug. In both species the biologic half-life of free levorphanol in the plasma was about 75 to 90 minutes, whereas the biologic half-life of conjugated levorphanol was about 3 hours.

About 2.5 per cent of the levorphanol administered to the monkey appeared in urine as free levorphanol and 35 per cent as conjugated levorphanol. In the dog, the percentage of free levorphanol in urine was somewhat higher, averaging 4.4 per cent, the conjugated levorphanol amounting to 42 per cent. Less than 0.1 per cent of the administered dose is excreted in the feces of either species.

The dog excretes a very small percentage of the radioactivity of the administered levorphanol as C14O2, although the rat eliminates about 5 per cent and the monkey about 20 per cent. The total radioactivity in monkey urine, and especially in rat urine, exceeds the total levorphanol (free plus conjugated).