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Identification
NameOndansetron
Accession NumberDB00904  (APRD00481)
Typesmall molecule
Groupsapproved
Description

A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties. [PubChem]

Structure
Thumb
SynonymsNot Available
Salts
Name/CAS Structure Properties
Ondansetron hydrochloride dihydrate
Thumb Not applicable DBSALT000921
Brand names
NameCompany
ZofranGlaxoSmithKline
Zofran ODTNot Available
ZophrenNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number99614-02-5
WeightAverage: 293.363
Monoisotopic: 293.152812245
Chemical FormulaC18H19N3O
InChI KeyInChIKey=FELGMEQIXOGIFQ-UHFFFAOYSA-N
InChI
InChI=1S/C18H19N3O/c1-12-19-9-10-21(12)11-13-7-8-16-17(18(13)22)14-5-3-4-6-15(14)20(16)2/h3-6,9-10,13H,7-8,11H2,1-2H3
IUPAC Name
9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-2,3,4,9-tetrahydro-1H-carbazol-4-one
SMILES
CN1C2=C(C3=CC=CC=C13)C(=O)C(CN1C=CN=C1C)CC2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIndoles and Derivatives
SubclassCarbazoles
Direct parentCarbazoles
Alternative parentsIndoles; N-substituted Imidazoles; Benzene and Substituted Derivatives; N-methylpyrroles; Ketones; Polyamines
Substituentsindole; n-substituted pyrrole; n-methylpyrrole; benzene; n-substituted imidazole; substituted pyrrole; azole; pyrrole; imidazole; ketone; polyamine; organonitrogen compound; amine; carbonyl group
Classification descriptionThis compound belongs to the carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
Pharmacology
IndicationFor the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, postoperation, and radiation. Also used for the treatment of postoperative nausea and vomiting.
PharmacodynamicsOndansetron is a highly specific and selective serotonin 5-HT3 receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors. The serontonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.
Mechanism of actionOndansetron is a selective serotonin 5-HT3 receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone.
AbsorptionOndansetron is well absorbed after oral administration and undergoes limited first-pass metabolism.
Volume of distributionNot Available
Protein binding70%-76% (Plasma protein binding)
Metabolism

Hepatic

Route of eliminationNot Available
Half life5.7 hours
Clearance
  • 0.38 L/h/kg [Normal Adult Volunteers (19-40 yrs)]
  • 0.32 L/h/kg [Normal Adult Volunteers (61-74 yrs)]
  • 0.26 L/h/kg [Normal Adult Volunteers (>=75 yrs)]
ToxicityLow blood pressure and fainting, sudden blindness, severe constipation
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9941
Blood Brain Barrier + 0.9882
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.7019
P-glycoprotein inhibitor I Inhibitor 0.5833
P-glycoprotein inhibitor II Inhibitor 0.8807
Renal organic cation transporter Inhibitor 0.7955
CYP450 2C9 substrate Non-substrate 0.7456
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Substrate 0.647
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5954
Ames test Non AMES toxic 0.5463
Carcinogenicity Non-carcinogens 0.9676
Biodegradation Not ready biodegradable 0.9884
Rat acute toxicity 2.4555 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7054
hERG inhibition (predictor II) Inhibitor 0.7926
Pharmacoeconomics
Manufacturers
  • Par pharmaceutical
  • Aurobindo pharma ltd
  • Barr laboratories inc
  • Glenmark generics ltd
  • Kv pharmaceutical co
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Sandoz inc
  • Sun pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Glaxosmithkline
  • Akorn strides llc
  • Apotex inc
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Emcure pharmaceuticals ltd
  • Gland pharma ltd
  • Hikma farmaceutica (portugal) sa
  • Hospira inc
  • Lannett holdings inc
  • Luitpold pharmaceuticals inc
  • Pharmaforce inc
  • Pliva hrvatska doo
  • Sandoz canada inc
  • Spectrum pharmaceuticals
  • Wockhardt ltd
  • Bedford laboratories
  • Claris lifesciences ltd
  • Teva parenteral medicines inc
  • Baxter healthcare corp
  • Apotex inc richmond hill
  • Taro pharmaceuticals ireland ltd
  • Roxane laboratories inc
  • Taro pharmaceutical industries ltd
  • Dr reddys laboratories ltd
  • Natco pharma ltd
  • West ward pharmaceutical corp
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous
LiquidOral
SolutionIntravenous
TabletOral
Prices
Unit descriptionCostUnit
Ondansetron 30 8 mg Dispersible Tablet Box1158.51USDbox
Zofran ODT 30 4 mg Dispersible Tablet Box782.26USDbox
Ondansetron 30 4 mg Dispersible Tablet Box695.53USDbox
Ondansetron hcl powder177.0USDg
Ondansetron hcl 24 mg tablet105.5USDtablet
Zofran 8 mg tablet45.16USDtablet
Zofran odt 8 mg tablet41.76USDtablet
Ondansetron hcl 8 mg tablet40.75USDtablet
Ondansetron odt 8 mg tablet37.13USDtablet
Zofran 4 mg tablet27.11USDtablet
Ondansetron hcl 4 mg tablet25.07USDtablet
Zofran odt 4 mg tablet25.07USDtablet
Zofran 8 mg Tablet23.02USDtablet
Zofran Odt 8 mg Disintegrating Tablet22.49USDtablet
Ondansetron odt 4 mg tablet22.3USDtablet
Zofran 4 mg Tablet15.09USDtablet
Zofran Odt 4 mg Disintegrating Tablet14.74USDtablet
Zofran 2 mg/ml vial12.82USDml
Zofran 4 mg/2 ml vial12.82USDml
Apo-Ondansetron 8 mg Tablet12.06USDtablet
Co Ondansetron 8 mg Tablet12.06USDtablet
Jamp-Ondansetron 8 mg Tablet12.06USDtablet
Mint-Ondansetron 8 mg Tablet12.06USDtablet
Mylan-Ondansetron 8 mg Tablet12.06USDtablet
Novo-Ondansetron 8 mg Tablet12.06USDtablet
Ondansetron-Odan 8 mg Tablet12.06USDtablet
Phl-Ondansetron 8 mg Tablet12.06USDtablet
Pms-Ondansetron 8 mg Tablet12.06USDtablet
Ran-Ondansetron 8 mg Tablet12.06USDtablet
Ratio-Ondansetron 8 mg Tablet12.06USDtablet
Sandoz Ondansetron 8 mg Tablet12.06USDtablet
Zofran 2 mg/ml11.12USDml
Apo-Ondansetron 4 mg Tablet7.9USDtablet
Co Ondansetron 4 mg Tablet7.9USDtablet
Jamp-Ondansetron 4 mg Tablet7.9USDtablet
Mint-Ondansetron 4 mg Tablet7.9USDtablet
Mylan-Ondansetron 4 mg Tablet7.9USDtablet
Novo-Ondansetron 4 mg Tablet7.9USDtablet
Ondansetron-Odan 4 mg Tablet7.9USDtablet
Phl-Ondansetron 4 mg Tablet7.9USDtablet
Pms-Ondansetron 4 mg Tablet7.9USDtablet
Ran-Ondansetron 4 mg Tablet7.9USDtablet
Ratio-Ondansetron 4 mg Tablet7.9USDtablet
Sandoz Ondansetron 4 mg Tablet7.9USDtablet
Ondansetron (Preservative Free) 2 mg/ml6.23USDml
Ondansetron (Preserved) 2 mg/ml6.23USDml
Ondansetron (Unpreserved) 2 mg/ml6.23USDml
Ondansetron (With Preservative) 2 mg/ml6.23USDml
Ondansetron Omega (Preservative Free) 2 mg/ml6.23USDml
Ondansetron Omega (With Preservative) 2 mg/ml6.23USDml
Ondansetron hcl 4 mg/2 ml vial3.13USDml
Zofran 0.8 mg/ml Solution2.3USDml
Apo-Ondansetron 0.8 mg/ml Solution1.53USDml
Ondansetron 32 mg/50 ml bag0.86USDml
Ondansetron hcl 32 mg/50 ml bg0.42USDml
Ondansetron 40 mg/20 ml vial0.17USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States58542701996-05-202016-05-20
United States53446581994-09-062011-09-06
Canada22056002000-05-302015-11-20
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP2.4Not Available
Predicted Properties
PropertyValueSource
water solubility2.48e-01 g/lALOGPS
logP2.56ALOGPS
logP2.35ChemAxon
logS-3.1ALOGPS
pKa (strongest acidic)15.39ChemAxon
pKa (strongest basic)7.34ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area39.82ChemAxon
rotatable bond count2ChemAxon
refractivity86.78ChemAxon
polarizability33.16ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
Spectra
References
Synthesis Reference

Peter Bod, Kalman Harsanyi, Ferenc Trischler, Eva Fekecs, Attila Csehi, Bela Hegedus, Eva Mersich nee Donat, Gyorgyi Szabo nee Komlosi, Erika Horvath nee Sziki, “Process for preparing ondansetron.” U.S. Patent US5478949, issued September, 1990.

US5478949
General Reference
  1. Ramsook C, Sahagun-Carreon I, Kozinetz CA, Moro-Sutherland D: A randomized clinical trial comparing oral ondansetron with placebo in children with vomiting from acute gastroenteritis. Ann Emerg Med. 2002 Apr;39(4):397-403. Pubmed
  2. Yilmaz HL, Yildizdas RD, Sertdemir Y: Clinical trial: oral ondansetron for reducing vomiting secondary to acute gastroenteritis in children—a double-blind randomized study. Aliment Pharmacol Ther. 2010 Jan;31(1):82-91. Epub . Pubmed
  3. Gregory RE, Ettinger DS: 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998 Feb;55(2):173-89. Pubmed
  4. Gan TJ: Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? CNS Drugs. 2005;19(3):225-38. Pubmed
External Links
ResourceLink
KEGG DrugD00456
KEGG CompoundC07325
PubChem Compound4595
PubChem Substance46504819
ChemSpider4434
BindingDB50000493
Therapeutic Targets DatabaseDAP000221
PharmGKBPA450705
IUPHAR2290
Guide to Pharmacology2290
Drug Product Database2239372
RxListhttp://www.rxlist.com/cgi/generic/ondansetron.htm
Drugs.comhttp://www.drugs.com/cdi/ondansetron.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/zof1501.shtml
WikipediaOndansetron
ATC CodesA04AA01
AHFS Codes
  • 56:22.20
PDB EntriesNot Available
FDA labelshow(126 KB)
MSDSshow(53.2 KB)
Interactions
Drug Interactions
Drug
AsenapineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
CrizotinibConcurrent use with crizotinib may decrease QTc interval. Consider alternative therapy.
Ezogabine Concurrent use of ezogabine and ondansetron can increase QTc interval. Consider alternate therapy.
IndacaterolBoth indacaterol and ondansetron prolong the QT interval. Consider alternate therapy.
PazopanibAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
TelavancinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
Food Interactions
  • Take without regard to meals.

1. 5-hydroxytryptamine receptor 3A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 3A P46098 Details

References:

  1. Artaiz I, Zazpe A, Del Rio J: Characterization of serotonergic mechanisms involved in the behavioural inhibition induced by 5-hydroxytryptophan in a modified light-dark test in mice. Behav Pharmacol. 1998 Mar;9(2):103-12. Pubmed
  2. Fortuno A, Ballaz S, Del Rio J, Barber A: CCK-mediated response in the activation of 5-HT receptor types in the guinea-pig ileum. J Physiol Biochem. 1999 Jun;55(2):85-92. Pubmed
  3. Llacer JM, Gallardo V, Delgado R, Parraga J, Martin D, Ruiz MA: X-ray diffraction and electron microscopy in the polymorphism study of ondansetron hydrochloride. Drug Dev Ind Pharm. 2001 Oct;27(9):899-908. Pubmed
  4. Carvalho F, Macedo D, Bandeira I, Maldonado I, Salles L, Azevedo MF, Rocha MA Jr, Fregoneze JB, De Castro-e-Silva E: Central 5-HT3 receptor stimulation by m-CPBG increases blood glucose in rats. Horm Metab Res. 2002 Feb;34(2):55-61. Pubmed
  5. Arcioni R, della Rocca M, Romano S, Romano R, Pietropaoli P, Gasparetto A: Ondansetron inhibits the analgesic effects of tramadol: a possible 5-HT spinal receptor involvement in acute pain in humans. Anesth Analg. 2002 Jun;94(6):1553-7, table of contents. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Gallardo Lara V, Gallardo ML, Morales Hernandez ME, Ruiz Martinez MA: Ondansetron: design and development of oral pharmaceutical suspensions. Pharmazie. 2009 Feb;64(2):90-3. Pubmed
  8. Mohan KC, Ravikumar K: Ondansetron hydrochloride: a competitive serotonin 5-HT3 receptor blocker. Acta Crystallogr C. 1995 Dec 15;51 ( Pt 12):2627-9. Pubmed
  9. Dimitrov DH: Effect of Ondansetron, a 5-HT Receptor Antagonist, on Fatigue in 2 Veterans With Hepatitis C. Prim Care Companion J Clin Psychiatry. 2009;11(6):366-7. Pubmed
  10. Szajewska H, Gieruszczak-Bialek D, Dylag M: Meta-analysis: ondansetron for vomiting in acute gastroenteritis in children. Aliment Pharmacol Ther. 2007 Feb 15;25(4):393-400. Pubmed
  11. Ramsook C, Sahagun-Carreon I, Kozinetz CA, Moro-Sutherland D: A randomized clinical trial comparing oral ondansetron with placebo in children with vomiting from acute gastroenteritis. Ann Emerg Med. 2002 Apr;39(4):397-403. Pubmed
  12. Gregory RE, Ettinger DS: 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998 Feb;55(2):173-89. Pubmed
  13. Gan TJ: Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? CNS Drugs. 2005;19(3):225-38. Pubmed

2. 5-hydroxytryptamine receptor 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 4 Q13639 Details

References:

  1. van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. Pubmed

3. Mu-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Mu-type opioid receptor P35372 Details

References:

  1. van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. Pubmed

4. 5-hydroxytryptamine receptor 1A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1A P08908 Details

References:

  1. van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. Pubmed

5. 5-hydroxytryptamine receptor 1B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1B P28222 Details

References:

  1. van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. Pubmed

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Janicki PK: Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Med Sci Monit. 2005 Oct;11(10):RA322-8. Epub 2005 Sep 26. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

5. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

6. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on October 04, 2013 13:24