Telotristat ethyl (LX1606) is a novel, orally-delivered inhibitor of tryptophan hydroxylase that reduces serotonin production.
LX1606 (15, 50, 150, 300 mg/kg, po, qd) reduces serotonin content in the periphery, but not in the brain of the mice. Telotristat ethyl (LX1606) (200 mg/kg po, qd) prevents the increase in blood neutrophil counts that is observed after TNBS challenge, provides significant protection in a mouse model of inflammatory bowel disease. LX1606 (200 mg/kg po, qd) protects the mouse IBD model confirmed by histopathology evaluation.
|Formulation||formulated in 15% cyclodextrin (Captisol, pH 3-4) or 0.25% methylcellulose|
|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||DMSO 10 mM|
Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine.
Margolis KG, et al. Gut. 2014 Jun;63(6):928-37. PMID: 23749550.
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