Chemical: Drug
granisetron

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PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

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The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for granisetron

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA No VIP available CYP2D6 *1 N/A N/A N/A
No VIP available CA No VIP available CYP2D6 *1xN N/A N/A N/A
No VIP available CA VA
rs10494366 NC_000001.10:g.162085685G>T, NC_000001.11:g.162115895G>T, NG_015979.1:g.51105G>T, NM_001164757.1:c.106-38510G>T, NM_014697.2:c.106-38510G>T, XR_922217.1:n.884-1993C>A, XR_922219.1:n.713-1993C>A, XR_922221.1:n.713-9147C>A, rs59845656
G > T
SNP
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • APF530
  • Granisetron HCl
  • Granisetron base
  • Granisetron hydrochloride
  • Granisetronum [INN-Latin]
Trade Names
  • Kytril
Brand Mixture Names

PharmGKB Accession Id

PA449809

Type(s):

Drug

Description

A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic and antinauseant for cancer chemotherapy patients.

Source: Drug Bank

Indication

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).

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Granisetron is a potent, selective antagonist of 5-HT 3 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.

Source: Drug Bank

Pharmacology

Granisetron is a selective inhibitor of type 3 serotonergic (5-HT 3) 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-HT 3 receptors. The serontonin 5-HT 3 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.

Source: Drug Bank

Food Interaction

Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

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.

Source: Drug Bank

Protein Binding

65%

Source: Drug Bank

Absorption

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

Source: Drug Bank

Half-Life

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

Source: Drug Bank

Toxicity

LD 50>2000 mg/kg (rat, oral)

Source: Drug Bank

Clearance

Route of Elimination

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

Source: Drug Bank

Chemical Properties

Chemical Formula

C18H24N4O

Source: Drug Bank

Isomeric SMILES

CN1[C@@H]2CCC[C@H]1C[C@@H](C2)NC(=O)C3=NN(C4=CC=CC=C43)C

Source: Drug Bank

CN1N=C(C(=O)NC2CC3CCCC(C2)N3C)C2=C1C=CC=C2

Source: Drug Bank

Canonical SMILES

CN1N=C(C(=O)NC2CC3CCCC(C2)N3C)C2=CC=CC=C12

Source: Drug Bank

Average Molecular Weight

312.4094

Source: Drug Bank

Monoisotopic Molecular Weight

312.19501141

Source: Drug Bank

SMILES

CN1N=C(C(=O)NC2CC3CCCC(C2)N3C)C2=CC=CC=C12

Source: Drug Bank

InChI String

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)

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ABCB1
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
CYP2D6
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
HTR3A
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
NOS1AP

Drug Targets

Gene Description
HTR3A (source: Drug Bank )
HTR6 (source: Drug Bank )
No related drugs are available.

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Prevent
Contraindicated With

Publications related to granisetron: 4

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
5 HT(3)-receptor antagonists and cardiac repolarization time in patients expressing a novel genetic target associated with baseline QTc interval abnormalities. Journal of clinical anesthesia. 2011. Quraishi Sadeq A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Serotonin type 3 receptor genes: HTR3A, B, C, D, E. Pharmacogenomics. 2008. Niesler Beate, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Prevention of postoperative nausea and vomiting with granisetron and dolasetron in relation to CYP2D6 genotype. Anesthesia and analgesia. 2006. Janicki Piotr K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association of the ABCB1 3435C>T polymorphism with antiemetic efficacy of 5-hydroxytryptamine type 3 antagonists. Clinical pharmacology and therapeutics. 2005. Babaoglu Melih O, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0378-1003-94
DrugBank:
DB00889
KEGG Compound:
C07023
KEGG Drug:
D04370
PubChem Compound:
3510
PubChem Substance:
46505137
9235
IUPHAR Ligand:
2292
2300
Drugs Product Database (DPD):
2088371
BindingDB:
50000483
ChemSpider:
3390
Therapeutic Targets Database:
DAP000295
FDA Drug Label at DailyMed:
8206d0ce-030e-4eb0-a1b2-16aeda592112

Clinical Trials

These are trials that mention granisetron and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.