Pharmacokinetics of the M1-agonist talsaclidine in mouse, rat, rabbit and monkey, and extrapolation to man

1. Talsaclidine is an M1-agonist under development for the treatment of Alzheimer's disease. The aim of the study was to investigate the absorption, distribution, metabolism and excretion (ADME) of single intravenous and oral doses of [14C]-talsaclidine in mouse, rat, rabbit and monkey. Previou...

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Veröffentlicht in:	Xenobiotica 2000, Vol.30 (8), p.797-814
Hauptverfasser:	Leusch, A., Troger, W., Greischel, A., Roth, W.
Format:	Artikel
Sprache:	eng
Schlagworte:	Alzheimer Disease - drug therapy Animals Biological and medical sciences Blood Proteins - metabolism Carbon Radioisotopes Female Haplorhini Humans Kinetics Male Medical sciences Metabolic Clearance Rate Mice Muscarinic Agonists - blood Muscarinic Agonists - pharmacokinetics Muscarinic Agonists - urine Neuropharmacology Pharmacology. Drug treatments Protein Binding Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Quinuclidines - blood Quinuclidines - pharmacokinetics Quinuclidines - urine Rabbits Rats Species Specificity talsaclidine
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Zusammenfassung:	1. Talsaclidine is an M1-agonist under development for the treatment of Alzheimer's disease. The aim of the study was to investigate the absorption, distribution, metabolism and excretion (ADME) of single intravenous and oral doses of [14C]-talsaclidine in mouse, rat, rabbit and monkey. Previous data in humans showed that the drug was mainly excreted into the urine as the unchanged parent drug. The hypothesis was tested if animal data of drugs, which are mainly excreted renally, could be extrapolated to human. 2. The apparent volume of distribution at steady-state (Vss) was comparable in all animal species (2-5 l.kg-1
ISSN:	0049-8254 1366-5928
DOI:	10.1080/00498250050119853