RANITIDINE BISMUTH CITRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H22N4O3S.C6H5O7.Bi
Molecular Weight	712.484
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Bi+3].OC(CC([O-])=O)(CC([O-])=O)C([O-])=O.CNC(NCCSCC1=CC=C(CN(C)C)O1)=C[N+]([O-])=O

InChI

InChIKey=XAUTYMZTJWXZHZ-IGUOPLJTSA-K

InChI=1S/C13H22N4O3S.C6H8O7.Bi/c1-14-13(9-17(18)19)15-6-7-21-10-12-5-4-11(20-12)8-16(2)3;7-3(8)1-6(13,5(11)12)2-4(9)10;/h4-5,9,14-15H,6-8,10H2,1-3H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);/q;;+3/p-3/b13-9+;;

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2667937,6309467

Ranitidine, a histamine H2-receptor antagonist, is now well established as a potent inhibitor of gastric acid secretion effective in the treatment and prophylaxis of gastrointestinal lesions aggravated by gastric acid secretion.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histamine H2 receptor 46 Target ID: P25102 Gene ID: 25461.0 Gene Symbol: Hrh2 Target Organism: Rattus norvegicus (Rat) Sources: http://www.pnas.org/content/93/13/6802.full.pdf	Antagonist 2778	0.14 µM [Ki]
Histamine H2 receptor 46 Target ID: P47747 Gene ID: NA Gene Symbol: HRH2 Target Organism: Cavia porcellus (Guinea pig) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9205741	Antagonist 2778	0.19 µM [Ki]
Histamine H2 receptor 46 Target ID: P25021 Gene ID: 3274.0 Gene Symbol: HRH2 Target Organism: Homo sapiens (Human) Sources: http://ca.gsk.com/media/592906/zantac.pdf	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Duodenal ulcer 42 Sources: http://ca.gsk.com/media/592906/zantac.pdf	Primary	Approved 8429	ZANTAC 150 Approved Use ZANTAC® (ranitidine hydrochloride) Tablets and Injection are indicated for the treatment of duodenal ulcer, benign gastric ulcer, reflux esophagitis, post-operative peptic ulcer, Zollinger-Ellison Syndrome, and other conditions where reduction of gastric secretion and acid output is desirable. These include the following: • the treatment of nonsteroidal anti-inflammatory drug (NSAID)- induced lesions, both ulcers and erosions, and their gastrointestinal (GI) symptoms and the prevention of their recurrence; • the prophylaxis of GI hemorrhage from stress ulceration in seriously ill patients; • the prophylaxis of recurrent hemorrhage from bleeding ulcers; • the prevention of Acid Aspiration Syndrome from general anaesthesia in patients considered to be at risk for this, including obstetrical patients in labour, and obese patients. In addition, ZANTAC® is indicated for the prophylaxis and maintenance treatment of duodenal or benign gastric ulcer in patients with a history of recurrent ulceration. Launch Date 1983
Gastric ulcer 67 Sources: http://ca.gsk.com/media/592906/zantac.pdf	Primary	Approved 8429	ZANTAC 150 Approved Use ZANTAC® (ranitidine hydrochloride) Tablets and Injection are indicated for the treatment of duodenal ulcer, benign gastric ulcer, reflux esophagitis, post-operative peptic ulcer, Zollinger-Ellison Syndrome, and other conditions where reduction of gastric secretion and acid output is desirable. These include the following: • the treatment of nonsteroidal anti-inflammatory drug (NSAID)- induced lesions, both ulcers and erosions, and their gastrointestinal (GI) symptoms and the prevention of their recurrence; • the prophylaxis of GI hemorrhage from stress ulceration in seriously ill patients; • the prophylaxis of recurrent hemorrhage from bleeding ulcers; • the prevention of Acid Aspiration Syndrome from general anaesthesia in patients considered to be at risk for this, including obstetrical patients in labour, and obese patients. In addition, ZANTAC® is indicated for the prophylaxis and maintenance treatment of duodenal or benign gastric ulcer in patients with a history of recurrent ulceration. Launch Date 1983
Gastroesophageal reflux disease 59 Sources: http://ca.gsk.com/media/592906/zantac.pdf	Primary	Approved 8429	ZANTAC 150 Approved Use ZANTAC® (ranitidine hydrochloride) Tablets and Injection are indicated for the treatment of duodenal ulcer, benign gastric ulcer, reflux esophagitis, post-operative peptic ulcer, Zollinger-Ellison Syndrome, and other conditions where reduction of gastric secretion and acid output is desirable. These include the following: • the treatment of nonsteroidal anti-inflammatory drug (NSAID)- induced lesions, both ulcers and erosions, and their gastrointestinal (GI) symptoms and the prevention of their recurrence; • the prophylaxis of GI hemorrhage from stress ulceration in seriously ill patients; • the prophylaxis of recurrent hemorrhage from bleeding ulcers; • the prevention of Acid Aspiration Syndrome from general anaesthesia in patients considered to be at risk for this, including obstetrical patients in labour, and obese patients. In addition, ZANTAC® is indicated for the prophylaxis and maintenance treatment of duodenal or benign gastric ulcer in patients with a history of recurrent ulceration. Launch Date 1983
Zollinger-Ellison syndrome 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018703s065,019675s031,020251s016lbl.pdf	Primary	Approved 8429	ZANTAC 150 Approved Use ZANTAC® (ranitidine hydrochloride) Tablets and Injection are indicated for the treatment of duodenal ulcer, benign gastric ulcer, reflux esophagitis, post-operative peptic ulcer, Zollinger-Ellison Syndrome, and other conditions where reduction of gastric secretion and acid output is desirable. These include the following: • the treatment of nonsteroidal anti-inflammatory drug (NSAID)- induced lesions, both ulcers and erosions, and their gastrointestinal (GI) symptoms and the prevention of their recurrence; • the prophylaxis of GI hemorrhage from stress ulceration in seriously ill patients; • the prophylaxis of recurrent hemorrhage from bleeding ulcers; • the prevention of Acid Aspiration Syndrome from general anaesthesia in patients considered to be at risk for this, including obstetrical patients in labour, and obese patients. In addition, ZANTAC® is indicated for the prophylaxis and maintenance treatment of duodenal or benign gastric ulcer in patients with a history of recurrent ulceration. Launch Date 1983

C_max

Value	Dose	Co-administered	Analyte	Population
440 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018703s068,019675s035,020251s019lbl.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		RANITIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
948.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6094785/	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		RANITIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.69 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6094785/	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		RANITIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018703s068,019675s035,020251s019lbl.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		RANITIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
85% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018703s068,019675s035,020251s019lbl.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		RANITIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg single, oral Highest studied dose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6329583/	healthy, adult n = 136 Health Status: healthy Age Group: adult Sex: M+F Population Size: 136 Sources: https://pubmed.ncbi.nlm.nih.gov/6329583/	Sources: https://pubmed.ncbi.nlm.nih.gov/6329583/
1500 mg single, oral Overdose Dose: 1500 mg Route: oral Route: single Dose: 1500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/28425352/	unknown, children n = 517 Health Status: unknown Age Group: children Sex: unknown Population Size: 517 Sources: https://pubmed.ncbi.nlm.nih.gov/28425352/	Sources: https://pubmed.ncbi.nlm.nih.gov/28425352/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737		inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 512 OCT2 647 OCT3 150 MATE1 306 MATE2 263 CYP3A 214 CYP1A2 1524	OCT1 327 OCT2 355 OCT3 80 P-gp 1537 FMO3 67 FMO1 17 CYP1A2 1054 CYP2A6 543 CYP2C19 991 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/	no
CYP3A 298	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/	no	no (co-administration study) Comment: Ranitidine has no effect on midazolam exposure Sources: https://pubmed.ncbi.nlm.nih.gov/10223772/
OCT3 150	inhibitor 3277 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	weak [IC50 290 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers	weak
OCT2 648	inhibitor 3277 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	yes [IC50 114 uM]
MATE1 308	inhibitor 3277 Sources: http://www.ncbi.nlm.nih.gov/pubmed/20053795	yes [IC50 18.9 uM]
OCT1 543	inhibitor 3277 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	yes [IC50 28 uM]
MATE2 263	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 25 uM]

Drug as victim

Target	Modality	Activity
FMO3 67	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	major
FMO1 17	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	minor
OCT2 355	substrate 3367 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	minor
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	no
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	no
OCT3 80	substrate 3367 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11128045/	yes
OCT1 327	substrate 3367 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16141367	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9862768/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8776	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8776
ChemicalBook	CB5480252	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5480252
MolPort	MolPort-003-666-370	https://www.molport.com/shop/molecule-link/MolPort-003-666-370
ZINC	ZINC000001530728	http://zinc15.docking.org/substances/ZINC000001530728

PubMed

Title	Date	PubMed
Comparison of ranitidine and high-dose antacid in the treatment of prepyloric or duodenal ulcer. A double-blind controlled trial.	1985 Jan	3887547
Mental confusion as a side effect of ranitidine.	1986 Feb	3946668
Fatal renal and hepatic toxicity after treatment with diltiazem.	1987 Nov 14	3120959
Reversible chorea due to ranitidine and cimetidine.	1988 Jul 16	2899203
Cardiac arrest associated with ranitidine.	1989 Aug 19	2507055
A dog model for acetaminophen-induced fulminant hepatic failure.	1989 Feb	2910762
Famotidine and ranitidine, but not cimetidine, cause severe, disabling headache.	1989 Feb	2563629
Histamine release in the isolated vascularly perfused stomach of the rat: regulation by autoreceptors.	1989 Mar	2470453
Effects of antihistaminics on locomotor activity in mice. Comparison with opiate and amphetamine-induced hyperactivity.	1991	1676005
Ranitidine pharmacokinetics and adverse central nervous system reactions.	1992 Nov	1444693
Ranitidine-related Stevens-Johnson syndrome in patients with severe liver diseases: a report of two cases.	2001 Apr	11354291
Nephrotoxicity and hepatotoxicity of histamine H2 receptor antagonists.	2001 Jan	11219486
Depression or hypoactive delirium? A report of ciprofloxacin-induced mental disorder in a patient with chronic obstructive pulmonary disease.	2001 Jan-Feb	11150940
Ranitidine-induced acute interstitial nephritis in a cadaveric renal allograft.	2001 Jul	11431197
Management of heartburn in a large, randomized, community-based study: comparison of four therapeutic strategies.	2001 Jun	11419818
Control of intragastric acidity with over-the-counter doses of ranitidine or famotidine.	2001 Oct	11563997
Regional differences in functional receptor distribution and calcium mobilization in the intact human lens.	2001 Sep	11527950
Functional analysis of histamine receptor subtypes involved in endothelium-mediated relaxation of the human uterine artery.	2002 Aug	12100006
Histamine H(2) -like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [(3) H]tiotidine binding.	2002 Jun	12065605
Drug points: Severe myalgia from an interaction between treatments with pantoprazole and methotrexate.	2002 Jun 22	12077038
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.	2004 Nov	15286053
Histamine H2-receptor antagonist ranitidine protects against neural death induced by oxygen-glucose deprivation.	2004 Oct	15322300
Carrier-mediated uptake of H2-receptor antagonists by the rat choroid plexus: involvement of rat organic anion transporter 3.	2004 Sep	15319347
Role of histamine in airway remodeling of asthmatic guinea pig.	2005 Dec 25	16344897
Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response.	2005 Jul	15995512
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Cimetidine induces interleukin-18 production through H2-agonist activity in monocytes.	2006 Aug	16723495
In vitro availability of metformin in presence of h(2) receptor antagonists.	2006 Jan	16632449
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.	2006 Mar	16291876
The role of tumor necrosis factor alpha in lipopolysaccharide/ranitidine-induced inflammatory liver injury.	2007 Nov	17698507
Gastroprotective and antioxidant effects of montelukast on indomethacin-induced gastric ulcer in rats.	2007 Sep	17895592
Protective effect of histamine H2 receptor antagonist ranitidine against rotenone-induced apoptosis.	2009 Nov	19723537
Two cases of h(2)-receptor antagonist hypersensitivity and cross-reactivity.	2011 Apr	21461253
Discovery of two clinical histamine H(3) receptor antagonists: trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and trans-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764).	2011 Nov 10	21928839
Gastroprotective effects of goniothalamin against ethanol and indomethacin-induced gastric lesions in rats: Role of prostaglandins, nitric oxide and sulfhydryl compounds.	2014 Dec 5	25451594

Patents

Sample Use Guides

In Vivo Use Guide

150 mg twice daily (tablets or syrup)

Route of Administration: Oral

In Vitro Use Guide

10uM ranitidine partially suppresses histamine-elicited signaling in human tubular epithelial cells

Name

Type

Language

RANITIDINE BISMUTH CITRATE

Official Name

English

RANITIDINE BISMUTH CITRATE [VANDF]

Common Name

English

1,2,3-PROPANETRICARBOXYLIC ACID, 2-HYDROXY-, BISMUTH(3+) SALT, COMPD. WITH N-(2-(((5-((DIMETHYLAMINO)METHYL)-2-FURANYL)METHYL)THIO)ETHYL)-N'-METHYL-2-NITRO-1,1-ETHENEDIAMINE (1:1:1)

Common Name

English

GR-122311X

Code

English

RANITIDINE BISMUTH CITRATE [USAN]

Common Name

English

RANITIDINE BISMUTH CITRATE [ORANGE BOOK]

Common Name

English

GR 122311X

Code

English

Ranitidine bismuth citrate [WHO-DD]

Common Name

English

TRITEC

Brand Name

English

RANITIDINE BISMUTH CITRATE [MI]

Common Name

English

RANITIDINE BISMUTH CITRATE [MART.]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QA02BA07