Molecule

Drug Groups

approved; withdrawn

Description

Alosetron is a 5-HT3 antagonist used only for the management of severe diarrhoea-predominant irritable bowel syndrome (IBS) in women. Alosetron has an antagonist action on the 5-HT3 receptors and thus may modulate serotonin-sensitive gastrointestinal (GI) processes. Alosetron was voluntarily withdrawn from the US market in November 2000 by the manufacturer due to numerous reports of severe adverse effects including ischemic colitis, severely obstructed or ruptured bowel, and death. In June 2002, the FDA approved a supplemental new drug application allowing the remarketing of the drug under restricted conditions of use.

Indication

Only for the treatment of symptoms of severe diarrhea-predominant irritable bowel syndrome (IBS) in women with chronic symptoms (generally lasting greater than 6 months) who does not present with anatomic or biochemical GI abnormalities and have not responded to conventional therapy.

Pharmacology

Alosetron is a potent and selective antagonist of the serotonin 5-HT₃ receptor type. Activation of these receptors and the resulting neuronal depolarization affects the regulation of visceral pain, colonic transit, and GI secretions processes that are related to IBS. By blocking these receptors, alosetron is able to effectively control IBS.

Affected Organisms

Biotransformation

Hepatic, via microsomal cytochrome P450 (CYP)

Absorption

50-60 %

Half Life

1.5 hours

Protein Binding

82%

Elimination

Renal elimination of unchanged alosetron accounts for only 6% of the dose. Alosetron is extensively metabolized in humans.

Distribution

* 65 to 95 L

Clearance

* 600 mL/min

References

External Links