Absorption, Distribution, Metabolism, and Elimination of Radiolabeled Xanomeline in Healthy Male Subjects

Abstract

Collaboration between scientists at Novo Nordisk Inc. and Eli Lilly and Company has produced xanomeline, one of the most selective M1 agonists known. In vitro pharmacologic activity demonstrated and defined the unique M1 agonist specificity associated with xanomeline. An increasing amount of data suggests that the M1 receptor system may be involved in the pathophysiology of the memory defect in Alzheimer’s disease. Clinical trials to evaluate the potential of xanomeline in the treatment of patients with Alzheimer’s Disease are in progress. In order to better understand the disposition of xanomeline in humans, we gave healthy volunteers a single 75 mg ¹⁴C xanomeline dose. This study describes the analysis of radioactivity in body fluids, the characterization of parent xanomeline/metabolites, and the pharmacokinetics of xanomeline and xanomeline metabolites.