Autoradiographic studies on the distribution of drugs. I. Distribution of 14C-anisotropine methbromide in mice.

Abstract

The distribution of 14C-anisotropine methbromide, a quaternary ammonium derivative of atropine, was studied in mice by whole-body autoradiographic technique. After i. p. and s. c. injections, the radioactivity was found to be mainly concentrated in the excretory organs : the liver, kidney, gall and urinary bladders, gastrointestinal tract and salivary gland, indicating a rapid excertion of the drug via both the urinary and biliary routes. In addition, the radioactivity was found to be accumulated specifically in the pancreas, gastric mucosa, walls of the spermatic and oviducts and uterus. Almost no accumulation was observed in the central nervous system, the muscular tissues and the endocrine organs. Autoradiography in mice of which the common bile duct was ligated prior to the injection showed an occurrence of a glandular secretion of the drug into the intestinal mucosa from the blood circulation. After oral administration, the radioactivity was found to be restricted very effectively to the gastrointestinal tract, indicating a limited absorption from the intestine, and the most part of the absorbed drug to be cleared back into the intestinal tract via the bile. These characteristics are discussed with respect to the structural characteristic of quaternary ammonium structure and the possible relations are pointed out between the sites of the drug accumulation and those of the pharmacological action where the drug has been clinically applied as a peripheral anti-spasmodic agent with a lower side effect than has atropine.