Article: Ondansetron

Ondansetron
Systematic (IUPAC) name
9-methyl-3-[(2-methyl-1H-imidazol-1-yl) methyl]-1,2,3,9-tetrahydrocarbazol-4-one
Identifiers
CAS number	99614-02-5
ATC code	A04AA01
PubChem	4595
DrugBank	APRD00481
Chemical data
Formula	C18H19N3O
Mol. weight	325.9 g/mol
Pharmacokinetic data
Bioavailability	~60%
Protein binding	70%-76%
Metabolism	Hepatic (CYP3A4, CYP1A2, CYP2D6)
Half life	5.7 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	B1(AU) B(US)
Legal status	S4(AU) POM(UK) ℞-only(US)
Routes	Oral, rectal, IV, IM

Ondansetron (INN) (IPA: [ɒnˈdænsɛˌtrɒn]) is a serotonin 5-HT₃ receptor antagonist used mainly to treat nausea and vomiting following chemotherapy. Its effects are thought to be on both peripheral and central nerves. One part is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata, the other is a blockage of serotonin receptors in the chemoreceptor trigger zone. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors.

The drug is administered 1–3 times daily, depending on the severity of nausea and/or vomiting. The normal dose for adults and children over the age of 12, is 8mg initially, followed by a second dose of 8mg, eight hours later. The drug is then administered once every 12 hours, usually not for more than 2-3 days. Following oral administration, it takes about 1.5–2 hours to reach maximum plasma concentrations. This drug is removed from the body by the liver and kidneys.

It is currently marketed by GlaxoSmithKline (GSK) under the trade name Zofran®; other manufacturers include Cipla Ltd. (Emeset), Gedeon Richter Ltd. (Emetron), and Zentiva a.s. (Ondemet). On May 29, 2006, Baxter Healthcare received tentative approval [1] to market its own label of Ondansetron Injection, USP, 8 mg/50 mL and 32 mg/50 mL iso-osmotic sodium chloride solution, after GSK's patent expires on December 24, 2006.

History

Ondansetron was developed around 1984 by scientists working at Glaxo's laboratories in London. After several attempts the company successfully filed for U.S. patent protection for the drug in 1986. U.S. Patent 4,695,578 was granted in September 1987 while U.S. Patent 4,753,789 was granted in June 1988. U.S. Patent 5,578,628, a divisional patent of U.S. Patent 4,753,789, was granted in November 26, 1996. Ondansetron was granted Food and Drug Administration (FDA) approval as Zofran in January 1991. Glaxo did pediatric research on Zofran's uses, gained patent extension as a result. Consequently U.S. exclusivity is now set to end December 24, 2006.

Clinical uses

• Chemotherapy-induced nausea and vomiting
  • 5-HT₃ receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting. Many times they are given intravenously about 30 minutes before beginning therapy.
• Post-operative and post-radiation nausea and vomiting
• Is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis

Although highly effective, its high cost limits its use to controlling postoperative nausea and vomiting (PONV) and chemotherapy-induced nausea and vomiting (CINV). It is also used off-label to treat hyperemesis gravidarum in pregnant women, but there is no conclusive data available on its safety in pregnancy, especially during the first trimester. It is also often used to treat cyclic vomiting syndrome although there have been no formal trials to confirm efficacy, case reports suggest it can be helpful in some cases.

Clinical effect of ondansetron (and other drugs from the same group) can be potentiated by combining it with dexamethasone.

Adverse effects

Ondansetron is a well-tolerated drug with few side effects. Headache, constipation, and dizziness are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drug's use. It is broken down by the hepatic cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system.

See also

• Granisetron
• Dolasetron
• Alosetron (not an antiemetic but another 5-HT₃ antagonist investigated for controlling irritable bowel syndrome)