Tiotropium Bromide hydrate 139404-48-1

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Molecular Weight: 490.43 Tiotropium Bromide hydrate is a monohydrate of tiotropium bromide (Spiriva; Tiova; BA 679BR; tiopropium) that is an anticholinergic and bronchodilator and a muscarinic receptor antagonist.

Tiotropium bromide is a potent muscarinic antagonist with equal affinity
for M1-, M2- and M3-receptors and is approximately 10-fold more potent
than ipratropium bromide. Tiotropium bromide has a potent inhibitory
effect against cholinergic nerve-induced contraction of guinea-pig and
human airways, that has a slower onset than atropine or ipratropium
bromide. Tiotropium bromide, ipratropium bromide and atropine all
increase ACh release on neural stimulation and that this effect is
washed out equally quickly for the three antagonists. Tiotropium bromide
dissociates slowly from M3-receptors (on airway smooth muscle) but
rapidly from M2 autoreceptors (on cholinergic nerve terminals). Tiotropium significantly inhibits the release of chemotactic substances by AM, MonoMac6 and A549 cells. Tiotropium bromide inhibits the Th2 cytokine production from PBMCs.

Tiotropium bromide significantly reduces airway inflammation and the Th2
cytokine production in bronchoalveolar lavage fluid (BALF) in both
acute and chronic mouse models of asthma. Tiotropium bromide
significantly decreases the goblet cell metaplasia, thickness of airway
smooth muscle, and airway fibrosis in a mouse model of asthma.
Tiotropium bromide reduces the levels of TGF-beta1 in BALF in a chronic
model. Tiotropium inhibits the increase in airway smooth
muscle mass, myosin expression, and contractility in a guinea pig model
of ongoing allergic asthma. Tiotropium abrogates the
LPS-induced increase in neutrophils, goblet cells, collagen deposition
and muscularised microvessels in a guinea pig model of chronic
obstructive pulmonary disease (COPD), but has no effect on emphysema.





Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

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.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

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