TD-4208 is a novel long-acting muscarinic antagonist currently in clinical development for the treatment of respiratory diseases, including bronchospasm due to COPD. The purpose of our studies was to characterize the in vivo bronchoprotective and antisialagogue effect of this new agent. In two preclinical species, we showed that inhaled TD-4208 produces sustained bronchoprotective activity up to 24 hours after dosing. Moreover, after 7-day repeat dosing in rats, equieffective bronchoprotective doses of TD-4208 inhibited salivation to a much lesser extent than the other two muscarinic antagonists. Thus, TD-4208 exhibits greater lung selectivity than either tiotropium or glycopyrronium.
|Dosages||3, 10, and 30 µg/kg|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||10 mM in DMSO|
Long acting muscarinic antagonists for the treatment of chronic obstructive pulmonary disease: a review of current and developing drugs.
Mastrodicasa MA, et al. Expert Opin Investig Drugs. 2017 Feb;26(2):161-174. PMID: 28004591.
In vivo pharmacological characterization of TD-4208, a novel lung-selective inhaled muscarinic antagonist with sustained bronchoprotective effect in experimental animal models.
Pulido-Rios MT, et al. J Pharmacol Exp Ther. 2013 Aug;346(2):241-50. PMID: 23685545.
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