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Identification
Name Ranitidine
Accession Number DB00863 (APRD00254)
Type small molecule
Groups approved
Description

A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Ranitidine Base
  • Ranitidine HCL
  • Ranitidine hydrochloride
  • Rantidine HCL
Brand names
  • Alquen
  • Alter-H2
  • Alvidina
  • Apo-Ranitidin
  • Artomil
  • Azuranit
  • Coralen
  • Digestosan
  • Ergan
  • Esofex
  • Fendibina
  • Gastrial
  • Gastridina
  • Gastrolav
  • Gastrosedol
  • Kuracid
  • Label
  • Lake
  • Logat
  • Melfax
  • Microtid
  • Mideran
  • Neugal
  • Noctone
  • Noktome
  • Normon
  • Novo-Radinine
  • Nu-Ranit
  • Pep-Rani
  • Ptinolin
  • Quadrin
  • Quantor
  • Radin
  • RAN
  • Ran H2
  • Ran Lich
  • Rani 2
  • Rani AbZ
  • Rani-BASF
  • Rani-nerton
  • Rani-Puren
  • Rani-Q
  • Rani-Sanorania
  • Raniben
  • Raniberl
  • Raniberta
  • Ranibloc
  • Ranic
  • Ranicux
  • Ranidil
  • Ranidin
  • Ranidine
  • Ranidura
  • Ranifur
  • Ranigasan
  • Ranigast
  • Ranigen
  • Ranilonga
  • Ranimerck
  • Raniogas
  • Raniplex
  • Ranisan
  • Ranitab
  • Ranitic
  • Ranitidin
  • Ranitidin 1A Pharma
  • Ranitidin AL
  • Ranitidin Arcana
  • Ranitidin Atid
  • Ranitidin AWD
  • Ranitidin Basics
  • Ranitidin Duncan
  • Ranitidin Dyna
  • Ranitidin Helvepharm
  • Ranitidin Heumann
  • Ranitidin Hexal
  • Ranitidin Merck
  • Ranitidin Millet
  • Ranitidin NM
  • Ranitidin Normon
  • Ranitidin PB
  • Ranitidin Stada
  • Ranitidin von ct
  • Ranitidin-Cophar
  • Ranitidin-Isis
  • Ranitidin-ratiopharm
  • Ranitidina predilu Grif
  • Ranitidina Tamarang
  • Ranitiget
  • Ranitin
  • Ranitine
  • Ranobel
  • Rantacid
  • Ranuber
  • Raticina
  • Regalil
  • Renatac
  • Rozon
  • Rubiulcer
  • Santanol
  • Serviradine
  • Sostril
  • Tanidina
  • Taural
  • Terposen
  • Toriol
  • Trigger
  • Ulcecur
  • Ulcex
  • Ulcirex
  • Ulcodin
  • Ulcolind Rani
  • Ulsaven
  • Ultidine
  • Viserul
  • Zandid
  • Zantac
  • Zantac 150
  • Zantac 75
  • Zantac In Plastic Container
  • Zantarac
  • Zantic
Brand name mixtures
  • Tritec (ranitidine bismuth citrate salt)
Categories
  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
CAS number 66357-35-5
Weight Average: 314.404
Monoisotopic: 314.141261280
Chemical Formula C13H22N4O3S
InChI Key InChIKey=VMXUWOKSQNHOCA-UKTHLTGXSA-N
InChI
InChI=1S/C13H22N4O3S/c1-14-13(9-17(18)19)15-6-7-21-10-12-5-4-11(20-12)8-16(2)3/h4-5,9,14-15H,6-8,10H2,1-3H3/b13-9+
Plain Text
IUPAC Name
dimethyl[(5-{[(2-{[(E)-1-(methylamino)-2-nitroethenyl]amino}ethyl)sulfanyl]methyl}furan-2-yl)methyl]amine
SMILES
CN\C(NCCSCC1=CC=C(CN(C)C)O1)=C/[N+]([O-])=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Furans
Substructures
  • Ethers
  • Oxoazaniums
  • Nitro compounds
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Furans
Pharmacology
Indication Used in the treatment of peptic ulcer disease (PUD), dyspepsia, stress ulcer prophylaxis, and gastroesophageal reflux disease (GERD).
Pharmacodynamics Ranitidine is a histamine H2-receptor antagonist similar to cimetidine and famotidine. An H2-receptor antagonist, often shortened to H2 antagonist, is a drug used to block the action of histamine on parietal cells in the stomach, decreasing acid production by these cells. These drugs are used in the treatment of dyspepsia, however their use has waned since the advent of the more effective proton pump inhibitors. Like the H1-antihistamines, the H2 antagonists are inverse agonists rather than true receptor antagonists.
Mechanism of action The H2 antagonists are competitive inhibitors of histamine at the parietal cell H2 receptor. They suppress the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid. They accomplish this by two mechanisms: histamine released by ECL cells in the stomach is blocked from binding on parietal cell H2 receptors which stimulate acid secretion, and other substances that promote acid secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells when the H2 receptors are blocked.
Absorption Approximately 50% bioavailability orally.
Volume of distribution
  • 1.4 L/kg
  • 1.76 L/kg [clinically significant renal function impairment (creatinine clearance 25 to 35 mL/min)]
Protein binding 15%
Metabolism

Hepatic. Ranitidine is metabolized to the N-oxide, S-oxide, and N-desmethyl metabolites, accounting for approximately 4%, 1%, and 1% of the dose, respectively.
Route of elimination The principal route of excretion is the urine (active tubular excretion, renal clearance 410mL/min), with approximately 30% of the orally administered dose collected in the urine as unchanged drug in 24 hours.
Half life 2.8-3.1 hours
Clearance
  • 29 mL/min [clinically significant renal function impairment]
  • 3 mL/min/Kg [neonatal patients]
Toxicity LD50=77mg/kg (orally in mice). Symptoms of overdose include muscular tremors, vomiting, and rapid respiration.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00230 Ranitidine Pathway SMP00230
Pharmacoeconomics
Manufacturers
  • Dr reddys laboratories ltd
  • Genpharm inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Glaxosmithkline
  • Bedford laboratories div ben venue laboratories inc
  • Ben venue laboratories inc
  • Alpharma us pharmaceuticals division
  • Amneal pharmaceuticals
  • Apotex inc
  • Aurobindo pharma usa inc
  • Cypress pharmaceutical inc
  • Pharmaceutical assoc inc div beach products
  • Ranbaxy laboratories ltd
  • Vintage pharmaceuticals inc
  • Wockhardt ltd
  • Boehringer ingelheim pharmaceuticals inc
  • Amneal pharmaceuticals ny llc
  • Boehringer ingelheim corp
  • Contract pharmacal corp
  • Dr reddys laboratories inc
  • Glenmark generics inc usa
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • L perrigo co
  • Ranbaxy pharmaceuticals inc
  • Torpharm inc
  • Watson laboratories inc
  • Wockhardt americas inc
  • Boehringer ingelheim
Packagers
Dosage forms
Form Route Strength
Solution Intravenous
Solution Oral
Tablet Oral
Prices
Unit description Cost Unit
Zantac 300 mg tablet 7.96 USD tablet
Ranitidine hcl powder 5.2 USD g
Zantac EFFERdose 25 mg Effervescent Tabs 4.18 USD tab
Zantac 25 efferdose tablet 4.02 USD tablet
Zantac 150 mg tablet 3.11 USD tablet
Ranitidine HCl 300 mg capsule 2.85 USD capsule
Ranitidine HCl 300 mg tablet 2.79 USD tablet
Ranitidine 300 mg tablet 2.69 USD tablet
Ranitidine hcl 25 mg/ml vial 2.0 USD ml
Zantac 25 mg/ml vial 2.0 USD ml
Ranitidine HCl 150 mg capsule 1.58 USD capsule
Zantac 25 mg/ml 1.58 USD ml
Ranitidine HCl 150 mg tablet 1.54 USD tablet
Ranitidine 150 mg tablet 1.48 USD tablet
Ranitidine 25 mg/ml 1.26 USD ml
Ranitidine HCl 15 mg/ml Syrup 1.0 USD ml
Ratio-Ranitidine 300 mg Tablet 0.82 USD tablet
Apo-Ranitidine 300 mg Tablet 0.82 USD tablet
Co Ranitidine 300 mg Tablet 0.82 USD tablet
Mylan-Ranitidine 300 mg Tablet 0.82 USD tablet
Nu-Ranit 300 mg Tablet 0.82 USD tablet
Pms-Ranitidine 300 mg Tablet 0.82 USD tablet
Ran-Ranitidine 300 mg Tablet 0.82 USD tablet
Zantac 15 mg/ml Syrup 0.81 USD ml
Zantac 75 tablet 0.49 USD tablet
Apo-Ranitidine 150 mg Tablet 0.42 USD tablet
Co Ranitidine 150 mg Tablet 0.42 USD tablet
Mylan-Ranitidine 150 mg Tablet 0.42 USD tablet
Nu-Ranit 150 mg Tablet 0.42 USD tablet
Pms-Ranitidine 150 mg Tablet 0.42 USD tablet
Ran-Ranitidine 150 mg Tablet 0.42 USD tablet
Ratio-Ranitidine 150 mg Tablet 0.42 USD tablet
Novo-Ranidine 300 mg Tablet 0.38 USD tablet
Phl-Ranitidine 300 mg Tablet 0.38 USD tablet
Sandoz Ranitidine 300 mg Tablet 0.38 USD tablet
Zantac 300 mg Tablet 0.38 USD tablet
Zantac 75 mg tablet 0.28 USD tablet
Wal-zan 75 mg tablet 0.27 USD tablet
Zantac 15 mg/ml Solution 0.23 USD ml
Ranitidine hcl 75 mg tablet 0.22 USD tablet
Sm acid reducer 75 mg tablet 0.22 USD tablet
Acid reducer 150 mg tablet 0.2 USD tablet
Wal-zan 75 tablet 0.2 USD tablet
Novo-Ranidine 150 mg Tablet 0.19 USD tablet
Phl-Ranitidine 150 mg Tablet 0.19 USD tablet
Sandoz Ranitidine 150 mg Tablet 0.19 USD tablet
Zantac 150 mg Tablet 0.19 USD tablet
CVS Pharmacy ranitidine 75 mg tablet 0.15 USD tablet
Apo-Ranitidine 15 mg/ml Solution 0.12 USD ml
Novo-Ranidine 15 mg/ml Solution 0.12 USD ml
Acid reducer 75 mg tablet 0.11 USD tablet
CVS Pharmacy acid reducer 75 mg tablet 0.11 USD tablet
Qc ranitidine 75 mg tablet 0.07 USD tablet
Patents
Country Patent Number Approved Expires
United States 5098715 1993-12-20 2010-12-20
United States 5102665 1992-12-23 2009-12-23
Canada 1332610 1994-10-18 2011-10-18
Properties
State solid
Melting point 69-70 oC
Experimental Properties
Property Value Source
water solubility 24.7 mg/mL PhysProp
logP 1.3 PhysProp
Caco2 permeability -6.31 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 7.95e-02 g/l ALOGPS
logP 0.79 ALOGPS
logP 0.98 ChemAxon Molconvert
logS -3.60 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 86.26 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 95.15 ChemAxon Molconvert
polarizability 33.60 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00422 Link_out
PubChem Compound 3001055 Link_out
PubChem Substance 46505543 Link_out
ChemSpider 2272523 Link_out
BindingDB 22893 Link_out
ChEBI 8776 Link_out
ChEMBL 8776 Link_out
Therapeutic Targets Database DAP000340 Link_out
PharmGKB PA451224 Link_out
Drug Product Database 740748 Link_out
RxList http://www.rxlist.com/cgi/generic2/ranitbc.htm Link_out
Drugs.com http://www.drugs.com/ranitidine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Ranitidine Link_out
ATC Codes
  • A02BA02
  • A02BA07
AHFS Codes
  • 56:28.12
PDB Entries Not Available
FDA label show (246.9 KB)
MSDS show (73.9 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.
  • Take without regard to meals.
Targets

1. Histamine H2 receptor

Pharmacological action: yes
Actions: antagonist

The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway

Organism class: human
UniProt ID: P25021 Link_out
Gene: HRH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Pattichis K, Louca LL: Histamine, histamine H2-receptor antagonists, gastric acid secretion and ulcers: an overview. Drug Metabol Drug Interact. 1995;12(1):1-36. Pubmed
Enzymes

1. Cytochrome P450 1A2

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

3. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

4. Cytochrome P450 3A4

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

5. Cytochrome P450 3A5

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Solute carrier family 22 member 1

Actions: inhibitor

Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

UniProt ID: O15245 Link_out
Gene: SLC22A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. Pubmed

2. Multidrug resistance protein 1

Actions: substrate, inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lentz KA, Polli JW, Wring SA, Humphreys JE, Polli JE: Influence of passive permeability on apparent P-glycoprotein kinetics. Pharm Res. 2000 Dec;17(12):1456-60. Pubmed
  2. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. Pubmed
  3. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. Pubmed
  4. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. Pubmed

3. Solute carrier family 22 member 8

Actions: substrate

Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tahara H, Kusuhara H, Chida M, Fuse E, Sugiyama Y: Is the monkey an appropriate animal model to examine drug-drug interactions involving renal clearance? Effect of probenecid on the renal elimination of H2 receptor antagonists. J Pharmacol Exp Ther. 2006 Mar;316(3):1187-94. Epub 2005 Nov 16. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.