Anticancer Drugs Oncology Pharmacology Physiotherapy Telotristat

Telotristat (Mechanism of Action)

In this article we will discuss Telotristat (Mechanism of Action)

In this article, we will discuss Telotristat (Mechanism of Action). So, let’s get started.

Mechanism of Action

Telotristat, the active metabolite of telotristat ethyl, is an inhibitor of tryptophan hydroxylase, which mediates the rate limiting step in serotonin biosynthesis. The in vitro inhibitory potency of telotristat towards tryptophan hydroxylase is 29 times higher than that of telotristat ethyl. Serotonin plays a role in mediating secretion, motility, inflammation, and sensation of the
gastrointestinal tract, and is over-produced in patients with carcinoid syndrome. Through inhibition of tryptophan hydroxylase, telotristat and telotristat ethyl reduce the production of peripheral serotonin, and the frequency of carcinoid syndrome diarrhea.


In healthy subjects, telotristat ethyl 500 mg three times daily (twice the recommended dosage) for 14 days decreased whole blood serotonin and 24-hour urinary 5-hydroxyindolacetic acid (u5­-HIAA) from baseline. A decrease in 24-hour u5-HIAA was observed as early as after 5 days of treatment. In patients with metastatic neuroendocrine tumors and carcinoid syndrome diarrhea, 24-hour u5­-HIAA decreased from baseline following 6 and 12 weeks of treatment with Telotristat 250 mg three times a day, whereas placebo did not decrease u5-HIAA.

Cardiac Electrophysiology
At a dose 6 times the recommended dose of 250 mg, Telotristat does not prolong the QT interval to any clinically relevant extent.

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