THE METABOLISM OF CHLORETHOXYBUTAMOXANE-C¹⁴

¹ The Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana

Samples of chlorbutamoxane labeled with radiocarbon in the O-ethyl group and in the N-butyl group have been prepared and their metabolism in several species studied.

In the rat the main route of metabolism was cleavage of the ether linkage. Ring hydroxylation degradation of the amino side-chain represented minor routes. In the dog the major pathway was found to be side-chain oxidation which resulted in the excretion in urine of 2-carboxy-5-chloro-8-ethoxy-1,4-benzodioxane as the dominant metabolite. Ring hydroxylation and ether cleavage were unimportant.

The metabolism in mice and guinea pigs followed that found in rats. In rabbits, however, the metabolic pattern resembled that found in dogs.

The in vivo pattern of metabolism of chlorethoxybutamoxane was found to be nearly identical to that of ethoxybutamoxane. Thus, it was not possible to attribute the increased duration of action shown by chlorethoxybutamoxane to an altered metabolism.