METABOLISM OF ADIPHENINE .1. ABSORPTION, DISTRIBUTION AND EXCRETION IN RATS AND MICE

The disposition of the anticholinergic, antihistaminic agent adiphenine labeled with 14C in 2 positions was investigated in rats and mice after i.v. administration, and was compared with that of the [14C]diethylethanolamine HCl and of the [14C]diphenylacetic acid. Radioactivity in the blood declined in a biphasic manner. Biliary elimination depended upon the 14C-labeled compound administered: < 5% dose for the diethylethanolamine moiety, 100% dose for the carboxylic moiety. Of the radioactivity appearing in rat bile > 1% is associated with unchanged adiphenine. In preliminary metabolic studies, 3 major metabolites were identified: diphenylacetic acid, diethylethanolamine and a diphenylacetic acid glucuronide. Uptake by the brain of [14C]adiphenine shortly after dosing is 15 times greater than that of blood. Radioactivity found in the hypophysis, the adrenals and melanoid pigments, with concentration up to 30 times greater than that found in the blood.