For the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy (including high dose cisplatin), postoperation, and radiation (including total body irradiation and daily fractionated abdominal radiation).

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Associated Conditions

Indication Type	Indication	Approval Level
Prevention of	Nausea and vomiting	••••••••••••
Treatment of	Nausea and vomiting	••• •••••
Prevention of	Nausea and vomiting	••• •••••
Prevention of	Nausea and vomiting	••••••••••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

Granisetron is a selective inhibitor of type 3 serotonergic (5-HT₃) receptors. Granisetron has little or no affinity for other serotonin receptors, including 5-HT 1 , 5-HT 1A , 5-HT 1B/C , or 5-HT 2 ; for alpha 1 -, alpha 2 -, or beta-adrenoreceptors; for dopamine D 2 receptors; for histamine H 1 receptors; for benzodiazepine receptors; for picrotoxin receptors; or for opioid receptors. In most human studies, granisetron has had little effect on blood pressure, heart rate, or electrocardiogram (ECG). The drug is structurally and pharmacologically related to ondansetron, another selective inhibitor of 5-HT₃ 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 action

Granisetron is a potent, selective antagonist of 5-HT₃ receptors. 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.

Target	Actions	Organism
A5-hydroxytryptamine receptor 3A	antagonist	Humans

Absorption

Absorption of is rapid and complete, though oral bioavailability is reduced to about 60% as a result of first pass metabolism.

Volume of distribution

Not Available

Protein binding

65%

Metabolism

Primarily hepatic; undergoes N -demethylation and aromatic ring oxidation followed by conjugation. Animal studies suggest that some of the metabolites may have 5-HT 3 receptor antagonist activity.

Hover over products below to view reaction partners

Granisetron
- 9'-desmethylgranisetron
- 7-hydroxygranisetron

Route of elimination

The remainder of the dose is excreted as metabolites, 48% in the urine and 38% in the feces.

Half-life

4-6 hours in healthy patients, 9-12 hours in cancer patients

Clearance

0.52 L/h/kg [Cancer Patients with 1 mg bid for 7 days]
0.41 L/h/kg [Healthy subject with a single 1 mg dose]

Adverse Effects

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Toxicity

LD₅₀>2000 mg/kg (rat, oral)

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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1,2-Benzodiazepine	The risk or severity of CNS depression can be increased when Granisetron is combined with 1,2-Benzodiazepine.
Abametapir	The serum concentration of Granisetron can be increased when it is combined with Abametapir.
Acenocoumarol	The risk or severity of adverse effects can be increased when Granisetron is combined with Acenocoumarol.
Acetazolamide	The risk or severity of CNS depression can be increased when Acetazolamide is combined with Granisetron.
Acetophenazine	The risk or severity of CNS depression can be increased when Granisetron is combined with Acetophenazine.

Food Interactions

Take with or without food. The absorption is unaffected by food.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Granisetron hydrochloride	318F6L70J8	107007-99-8	QYZRTBKYBJRGJB-WQTKJZBYSA-N

Product Images

International/Other Brands

Kevatril / Sancuso / Sustol

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Granisetron Hydrochloride Injection	Liquid	1 mg / mL	Intravenous	Sandoz Canada Incorporated	2009-02-20	2019-08-01
Granisetron Hydrochloride Injection	Solution	1 mg / mL	Intravenous	Strides Pharma Canada Inc	Not applicable	Not applicable
Granisetron Hydrochloride Injection	Liquid	1 mg / mL	Intravenous	Omega Laboratories Ltd	2009-05-14	Not applicable
Granisetron Hydrochloride Injection Sdz	Solution	1 mg / mL	Intravenous	Sandoz Canada Incorporated	2012-12-19	2019-08-01
Kytril	Injection, solution	1 mg/4mL	Intravenous	Genentech, Inc.	1993-12-29	2011-11-30

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Apo-granisetron	Tablet	1 mg	Oral	Apotex Corporation	2009-02-20	Not applicable
Granisetron	Injection	1 mg/1mL	Intravenous	Sandoz Inc.	2008-06-30	2020-05-19
Granisetron	Injection, solution	1 mg/1mL	Intravenous	Fresenius Kabi USA, LLC	2009-11-20	Not applicable
Granisetron	Injection, solution	1 mg/1mL	Intravenous	Fresenius Kabi USA, LLC	2009-11-20	2024-05-31
Granisetron	Injection	1 mg/1mL	Intravenous	Sandoz Inc.	2008-06-30	2020-05-19

Chemical Identifiers

UNII: WZG3J2MCOL
CAS number: 109889-09-0
InChI Key: MFWNKCLOYSRHCJ-BTTYYORXSA-N
InChI: InChI=1S/C18H24N4O/c1-21-13-6-5-7-14(21)11-12(10-13)19-18(23)17-15-8-3-4-9-16(15)22(2)20-17/h3-4,8-9,12-14H,5-7,10-11H2,1-2H3,(H,19,23)/t12-,13+,14-
IUPAC Name: 1-methyl-N-[(1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl]-1H-indazole-3-carboxamide
SMILES: CN1N=C(C(=O)N[C@@H]2C[C@@H]3CCC[C@H](C2)N3C)C2=C1C=CC=C2

References

Synthesis Reference

Neal Ward, David Alan Jones, Victor Witold Jacewicz, "Process for the preparation of granisetron." U.S. Patent US6268498, issued April, 1986.

US6268498

General References

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. [Article]
Tan M: Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2003 Sep;4(9):1563-71. [Article]
Feyer P, Seegenschmiedt MH, Steingraeber M: Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies. Support Care Cancer. 2005 Sep;13(9):671-8. Epub 2005 Jul 26. [Article]

External Links

KEGG Drug: D04370
KEGG Compound: C07023
PubChem Compound: 5284566
PubChem Substance: 46505137
ChemSpider: 10482033
BindingDB: 50443668
RxNav: 26237
ChEBI: 5537
ChEMBL: CHEMBL1290003
ZINC: ZINC000100018854
Therapeutic Targets Database: DAP000295
PharmGKB: PA449809
Guide to Pharmacology: GtP Drug Page
PDBe Ligand: CWB
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Granisetron

PDB Entries

2yme / 6np0

FDA label

Download (77.3 KB)

MSDS

Download (51.7 KB)

Clinical Trials

Clinical Trials Clinical Trial & Rare Diseases Add-on Data Package Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package

Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
Unlock 175K+ rows when you subscribe.View sample data
Not Available	Completed	Not Available	Complications; Cesarean Section / Hypotension	1	somestatus	stop reason	just information to hide
Not Available	Completed	Prevention	Post Operative Nausea and Vomiting (PONV)	2	somestatus	stop reason	just information to hide
Not Available	Completed	Supportive Care	Breast Cancer / Chronic Myeloproliferative Disorders / Gestational Trophoblastic Neoplasia / Leukemias / Lymphoma / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndrome / Myeloproliferative/Myelodysplastic Neoplasm / Nausea and vomiting / Neuroblastoma (NB) / Ovarian Cancer / Testicular Germ Cell Tumors	1	somestatus	stop reason	just information to hide
Not Available	Completed	Treatment	Nausea and Vomiting in Pediatric Age Group	1	somestatus	stop reason	just information to hide
Not Available	Completed	Treatment	Nausea / Vomiting	2	somestatus	stop reason	just information to hide

Pharmacoeconomics

Manufacturers

Strakan international ltd
Akorn inc
App pharmaceuticals llc
Baxter healthcare corp anesthesia and critical care
Bedford laboratories
Claris lifesciences ltd
Dr reddys laboratories inc
Ebewe pharma
Sagent strides llc
Sandoz canada inc
Teva parenteral medicines inc
Watson laboratories inc
Wockhardt usa inc
App pharmaceuticals
Hikma farmaceutica (portugal) sa
Hoffmann la roche inc
Cypress pharmaceutical inc
Apotex inc
Barr laboratories inc
Cipla ltd
Corepharma llc
Dr reddys laboratories ltd
Mylan pharmaceuticals inc
Natco pharma ltd
Orchid healthcare
Roxane laboratories inc
Taro pharmaceuticals usa inc
Teva pharmaceuticals usa

Packagers

Akorn Inc.
Amerigen Pharmaceuticals Inc.
Apotex Inc.
APP Pharmaceuticals
Ascend Laboratories LLC
Aveva Drug Delivery Systems Inc.
Baxter International Inc.
Bedford Labs
Ben Venue Laboratories Inc.
Cipla Ltd.
Corepharma LLC
Cura Pharmaceutical Co. Inc.
DAVA Pharmaceuticals
Doctor Reddys Laboratories Ltd.
Ebewe Pharma
F Hoffmann La Roche Ltd.
F Hoffmann-La Roche Ltd.
GlaxoSmithKline Inc.
Hawthorn Pharmaceuticals
Hikma Pharmaceuticals
Mylan
Neuman Distributors Inc.
Northstar Rx LLC
Orchid Healthcare
Physicians Total Care Inc.
Prostrakan Inc.
Roxane Labs
Taro Pharmaceuticals USA
Teva Pharmaceutical Industries Ltd.
UDL Laboratories
West-Ward Pharmaceuticals
Wockhardt Ltd.

Dosage Forms

Form	Route	Strength
Injection	Parenteral	1 MG/ML
Tablet	Oral	1 mg
Tablet	Oral	1.0 mg
Injection	Parenteral	3 mg/3ml
Injection		3 MG/ML
Injection	Intravenous
Solution	Intravenous	1 mg
Injection, solution		3 mg/3ml
Injection, solution
Tablet, film coated	Oral	1120 MG
Injection, solution	Intravenous bolus; Intravenous drip	1 MG/ML
Solution	Parenteral	1 MG/1ML
Solution	Parenteral	3 MG/3ML
Tablet, film coated	Oral	1 MG
Injection, solution		1 MG/ML
Injection, solution, concentrate	Intravenous; Parenteral	1 MG/ML
Solution	Parenteral	1 MG/ML
Injection	Intravenous	0.1 mg/1mL
Injection	Intravenous	1 mg/1mL
Injection	Intravenous	4 mg/4mL
Injection, solution	Intravenous	1.12 mg/1mL
Injection, solution	Intravenous	4 mg/4mL
Solution	Intravenous	1 mg/1mL
Solution	Intravenous	4 mg/4mL
Tablet	Oral	1 mg/1
Liquid	Intravenous	1 mg / mL
Solution	Intravenous	1 mg / mL
Solution, concentrate	Parenteral	1 MG/ML
Injection, solution	Parenteral	1 MG/1ML
Injection		3 mg/3ml
Injection, solution	Parenteral	3 MG/3ML
Solution	Intravenous	1 mg/ml
Tablet, film coated	Oral
Injection, solution	Intramuscular; Intravenous	1 mg/ml
Solution	Intravenous
Solution	Oral	2 mg/10mL
Injection, solution	Intravenous	3 mg/3ml
Solution		1 mg/ml
Injection		1.12 mg/ml
Solution	Parenteral	1 mg
Injection, solution	Intramuscular; Parenteral	3 MG/1ML
Injection, solution	Intravenous	0.1 mg/1mL
Injection, solution	Intravenous	1 mg/1mL
Injection, solution	Intravenous	1 mg/4mL
Injection, solution	Intravenous; Parenteral	1 MG/1ML
Injection, solution	Intravenous; Parenteral	3 MG/3ML
Injection, solution	Intravenous; Parenteral	3 MG/5ML
Solution	Oral	0.2 MG/ML
Tablet, film coated	Oral	1 mg/1
Injection, solution	Parenteral	3 mg
Solution	Intravenous	3 mg/3ml
Injection	Intravenous	1 mg/ml
Injection	Intravenous	3 mg/3ml
Solution	Parenteral	300000 mg
Tablet, film coated	Oral	2 mg
Injection		1 MG/ML
Solution, concentrate	Parenteral
Solution	Parenteral	3 MG
Patch	Transdermal	3.1 mg/24h
Patch	Transdermal	3.1 MG
Patch, extended release	Transdermal	34.3 mg
Solution
Solution	Intravenous	1.12 mg
Solution	Intravenous	3.000 mg
Injection	Subcutaneous	10 mg/0.4mL
Injection, solution	Intramuscular
Injection, solution	Intravenous
Solution	Oral
Tablet	Oral
Solution	Parenteral
Solution	Intravenous	1.00 mg
Injection	Parenteral
Solution		3 mg/3mL
Tablet	Oral	1.000 mg

Prices

Unit description	Cost	Unit
Sancuso 3.1 mg/24 hr patch	372.0USD	patch
Kytril 2 1 mg tablet Box	131.98USD	box
Kytril 1 mg tablet	62.94USD	tablet
Granisetron hcl 1 mg tablet	60.19USD	tablet
Granisetron hcl 4 mg/4 ml vial	24.0USD	ml
Kytril 1 mg Tablet	20.27USD	tablet
Apo-Granisetron 1 mg Tablet	14.14USD	tablet
Kytril 0.1 mg/ml vial	11.54USD	ml
Granisetron hcl 0.1 mg/ml vial	7.2USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
CA2158354	No	2004-07-13	2014-03-15
CA2100777	No	2003-08-19	2012-01-16
US7608282	No	2009-10-27	2024-10-22
US5952340	No	1999-09-14	2016-09-14
US6613355	No	2003-09-02	2021-06-28
US6790458	No	2004-09-14	2021-05-11
US8715710	No	2014-05-06	2024-09-28
US8252304	No	2012-08-28	2024-09-28
US8252305	No	2012-08-28	2024-09-28
US9913910	No	2018-03-13	2024-09-28
US10357570	No	2019-07-23	2024-09-28

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	219 °C (HCl salt)	Not Available
logP	2.6	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.434 mg/mL	ALOGPS
logP	2.64	ALOGPS
logP	1.88	Chemaxon
logS	-2.9	ALOGPS
pKa (Strongest Acidic)	14.75	Chemaxon
pKa (Strongest Basic)	9	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	3	Chemaxon
Hydrogen Donor Count	1	Chemaxon
Polar Surface Area	50.16 Å²	Chemaxon
Rotatable Bond Count	2	Chemaxon
Refractivity	101.83 m³·mol^-1	Chemaxon
Polarizability	35.57 Å³	Chemaxon
Number of Rings	4	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9947
Blood Brain Barrier	+	0.9515
Caco-2 permeable	+	0.5231
P-glycoprotein substrate	Substrate	0.5473
P-glycoprotein inhibitor I	Inhibitor	0.6287
P-glycoprotein inhibitor II	Inhibitor	0.7243
Renal organic cation transporter	Non-inhibitor	0.5895
CYP450 2C9 substrate	Non-substrate	0.7898
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Substrate	0.6978
CYP450 1A2 substrate	Non-inhibitor	0.8546
CYP450 2C9 inhibitor	Non-inhibitor	0.9019
CYP450 2D6 inhibitor	Non-inhibitor	0.8841
CYP450 2C19 inhibitor	Non-inhibitor	0.9073
CYP450 3A4 inhibitor	Non-inhibitor	0.8355
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.6016
Ames test	Non AMES toxic	0.5878
Carcinogenicity	Non-carcinogens	0.8464
Biodegradation	Not ready biodegradable	0.9868
Rat acute toxicity	2.3943 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9083
hERG inhibition (predictor II)	Inhibitor	0.5458

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-03di-0009000000-775096476371af54ef72
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03di-0209000000-7e27a19ff60407e27c5f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-03di-0029000000-8ce3b7b737db8386d04c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03di-3009000000-ee8fa73e1d03d45f3da7
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0n2c-1920000000-241b3671c602cba62b06
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0f6x-9720000000-4d7f3f6dd26fb5714ede
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	185.0252882	predicted	DarkChem Lite v0.1.0
[M-H]-	175.57648	predicted	DeepCCS 1.0 (2019)
[M+H]+	184.7835882	predicted	DarkChem Lite v0.1.0
[M+H]+	177.93448	predicted	DeepCCS 1.0 (2019)
[M+Na]+	184.6659882	predicted	DarkChem Lite v0.1.0
[M+Na]+	184.76445	predicted	DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.

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Property	Measurement	pH	Temperature (°C)	References
Kd (nM)	7.94	N/A	N/A	A29189
Kd (nM)	0.126	N/A	N/A	A29189
Kd (nM)	0.02	N/A	N/A	A29189
Ki (nM)	1.45	N/A	N/A	A29190 / A29192
Ki (nM)	3.98	N/A	N/A	A29191

Details1. 5-hydroxytryptamine receptor 3A

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons
Specific Function: excitatory extracellular ligand-gated monoatomic ion channel activity
Gene Name: HTR3A
Uniprot ID: P46098
Uniprot Name: 5-hydroxytryptamine receptor 3A
Molecular Weight: 55279.835 Da

References

Hillsley K, Grundy D: Plasticity in the mesenteric afferent response to cisplatin following vagotomy in the rat. J Auton Nerv Syst. 1999 May 28;76(2-3):93-8. [Article]
Turvill JL, Connor P, Farthing MJ: The inhibition of cholera toxin-induced 5-HT release by the 5-HT(3) receptor antagonist, granisetron, in the rat. Br J Pharmacol. 2000 Jul;130(5):1031-6. [Article]
Cappelli A, Anzini M, Vomero S, Mennuni L, Makovec F, Doucet E, Hamon M, Menziani MC, De Benedetti PG, Giorgi G, Ghelardini C, Collina S: Novel potent 5-HT(3) receptor ligands based on the pyrrolidone structure: synthesis, biological evaluation, and computational rationalization of the ligand-receptor interaction modalities. Bioorg Med Chem. 2002 Mar;10(3):779-801. [Article]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
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. [Article]
Tan M: Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2003 Sep;4(9):1563-71. [Article]
Ho KY, Gan TJ: Pharmacology, pharmacogenetics, and clinical efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Curr Opin Anaesthesiol. 2006 Dec;19(6):606-11. [Article]
Abdelsayed GG: Management of radiation-induced nausea and vomiting. Exp Hematol. 2007 Apr;35(4 Suppl 1):34-6. [Article]
Feyer P, Seegenschmiedt MH, Steingraeber M: Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies. Support Care Cancer. 2005 Sep;13(9):671-8. Epub 2005 Jul 26. [Article]

Enzymes

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function: 1,8-cineole 2-exo-monooxygenase activity
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Tan M: Granisetron: new insights into its use for the treatment of chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2003 Sep;4(9):1563-71. [Article]
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. [Article]
Nakamura H, Ariyoshi N, Okada K, Nakasa H, Nakazawa K, Kitada M: CYP1A1 is a major enzyme responsible for the metabolism of granisetron in human liver microsomes. Curr Drug Metab. 2005 Oct;6(5):469-80. [Article]

Details2. Cytochrome P450 1A1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
Specific Function: arachidonic acid monooxygenase activity
Gene Name: CYP1A1
Uniprot ID: P04798
Uniprot Name: Cytochrome P450 1A1
Molecular Weight: 58164.815 Da

References

Nakamura H, Ariyoshi N, Okada K, Nakasa H, Nakazawa K, Kitada M: CYP1A1 is a major enzyme responsible for the metabolism of granisetron in human liver microsomes. Curr Drug Metab. 2005 Oct;6(5):469-80. [Article]
Bustos ML, Zhao Y, Chen H, Caritis SN, Venkataramanan R: Polymorphisms in CYP1A1 and CYP3A5 Genes Contribute to the Variability in Granisetron Clearance and Exposure in Pregnant Women with Nausea and Vomiting. Pharmacotherapy. 2016 Dec;36(12):1238-1244. doi: 10.1002/phar.1860. Epub 2016 Dec 5. [Article]
Lang D, Radtke M, Bairlein M: Highly Variable Expression of CYP1A1 in Human Liver and Impact on Pharmacokinetics of Riociguat and Granisetron in Humans. Chem Res Toxicol. 2019 Jun 17;32(6):1115-1122. doi: 10.1021/acs.chemrestox.8b00413. Epub 2019 Apr 16. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 07, 2024 17:52

Granisetron

Identification

Structure for Granisetron (DB00889)

Pharmacology

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Clinical Trial & Rare Diseases Add-on Data Package

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Enzymes

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