NEDOCROMIL CALCIUM

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H15NO7.Ca
Molecular Weight	409.403
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Ca++].CCCC1=C2OC(=CC(=O)C2=CC3=C1N(CC)C(=CC3=O)C([O-])=O)C([O-])=O

InChI

InChIKey=FGUNXXYEYHFDNX-UHFFFAOYSA-L

InChI=1S/C19H17NO7.Ca/c1-3-5-9-16-10(13(21)7-12(18(23)24)20(16)4-2)6-11-14(22)8-15(19(25)26)27-17(9)11;/h6-8H,3-5H2,1-2H3,(H,23,24)(H,25,26);/q;+2/p-2

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021009s010lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB00716 | https://www.drugs.com/ppa/nedocromil-sodium.html | http://reference.medscape.com/drug/alocril-nedocromil-ophthalmic-999594

Nedocromil is a medication considered as mast cell stabilizer used to treat itching associated with allergic conjunctivitis. Nedocromil has been shown to inhibit the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets. Nedocromil inhibits activation and release of inflammatory mediators such as histamine, prostaglandin D2 and leukotrienes c4 from different types of cells in the lumen and mucosa of the bronchial tree. These mediators are derived from arachidonic acid metabolism through the lipoxygenase and cyclo-oxygenase pathways. The mechanism of action of nedocromil may be due partly to inhibition of axon reflexes and release of sensory neuropeptides, such as substance P, neurokinin A, and calcitonin-geneñrelated peptides. The result is inhibition of bradykinin-induced bronchoconstriction. Nedocromil does not possess any bronchodilator, antihistamine, or corticosteroid activity. Nedocromil is indicated for the treatment of itching associated with allergic conjunctivitis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
eosinophil chemotaxis 6 Target ID: GO:0048245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9150324	Inhibitor 8297
mast cell degranulation 7 Target ID: GO:0043303 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26803520	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Itching associated with allergic conjunctivitis 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021009s010lbl.pdf	Primary		Approved 8429	TILADE Approved Use ALOCRIL ® ophthalmic solution is indicated for the treatment of itching associated with allergic conjunctivitis. Launch Date 1992
Asthma 241 Sources: https://www.drugs.com/ppa/nedocromil-sodium.html	Primary		Approved 8429	TILADE Approved Use ALOCRIL ® ophthalmic solution is indicated for the treatment of itching associated with allergic conjunctivitis. Launch Date 1992

C_max

Value	Dose	Analyte	Population
13.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	6 μg/kg bw single, intravenous dose: 6 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.1 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020750ap_Tilade_clinphrmr.pdf	4 mg single, respiratory dose: 4 mg route of administration: Respiratory experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	70.5 mg single, oral dose: 70.5 mg route of administration: Oral experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	4 mg single, respiratory dose: 4 mg route of administration: Respiratory experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.6 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020750ap_Tilade_clinphrmr.pdf	20 mg single, respiratory dose: 20 mg route of administration: Respiratory experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	4 mg single, respiratory dose: 4 mg route of administration: Respiratory experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
13.4 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020750ap_Tilade_clinphrmr.pdf	0.42 mg single, intravenous dose: 0.42 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
10.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	6 μg/kg bw single, intravenous dose: 6 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.6 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020750ap_Tilade_clinphrmr.pdf	4 mg single, respiratory dose: 4 mg route of administration: Respiratory experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
49.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	70.5 mg single, oral dose: 70.5 mg route of administration: Oral experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	4 mg single, respiratory dose: 4 mg route of administration: Respiratory experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6.2 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020750ap_Tilade_clinphrmr.pdf	20 mg single, respiratory dose: 20 mg route of administration: Respiratory experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	4 mg single, respiratory dose: 4 mg route of administration: Respiratory experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8.9 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020750ap_Tilade_clinphrmr.pdf	0.42 mg single, intravenous dose: 0.42 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
21.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	70.5 mg single, oral dose: 70.5 mg route of administration: Oral experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	4 mg single, respiratory dose: 4 mg route of administration: Respiratory experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2825746/	4 mg single, respiratory dose: 4 mg route of administration: Respiratory experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
31.6 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020750ap_Tilade_clinphrmr.pdf	0.42 mg single, intravenous dose: 0.42 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NEDOCROMIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 % 2 times / day multiple, ophthalmic Highest studied dose Dose: 2 %, 2 times / day Route: ophthalmic Route: multiple Dose: 2 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21009lbl.pdf Page: CR 1957	unhealthy, 12-61 n = 289 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: 12-61 Sex: M+F Population Size: 289 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21009lbl.pdf Page: CR 1957	Disc. AE: Eyeball itching, Swelling... AEs leading to discontinuation/dose reduction: Eyeball itching Swelling Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21009lbl.pdf Page: CR 1957

AEs

AE	Significance	Dose	Population
Eyeball itching	Disc. AE	2 % 2 times / day multiple, ophthalmic Highest studied dose Dose: 2 %, 2 times / day Route: ophthalmic Route: multiple Dose: 2 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21009lbl.pdf Page: CR 1957	unhealthy, 12-61 n = 289 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: 12-61 Sex: M+F Population Size: 289 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21009lbl.pdf Page: CR 1957
Swelling	Disc. AE	2 % 2 times / day multiple, ophthalmic Highest studied dose Dose: 2 %, 2 times / day Route: ophthalmic Route: multiple Dose: 2 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21009lbl.pdf Page: CR 1957	unhealthy, 12-61 n = 289 Health Status: unhealthy Condition: allergic conjunctivitis Age Group: 12-61 Sex: M+F Population Size: 289 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21009lbl.pdf Page: CR 1957

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 270 UGT 192

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021009s010lbl.pdf#page=1 Page: 1.0	no
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021009s010lbl.pdf#page=1 Page: 1.0	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7492	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7492
ChemicalBook	CB9122310	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9122310
MolPort	MolPort-006-167-614	https://www.molport.com/shop/molecule-link/MolPort-006-167-614
ZINC	ZINC000003782807	http://zinc15.docking.org/substances/ZINC000003782807

PubMed

Title	Date	PubMed
Choosing therapy for childhood asthma.	2001	11772152
Bronchial, alveolar, and vascular-induced anaphylaxis and irritant-induced cardiovascular and pulmonary responses.	2001 Aug	11544156
Nedocromil sodium inhibits histamine-induced itch and flare in human skin.	2001 Feb	11159712
Asthma in the hospitalized obstetrical patient.	2001 Jun	11413902
Exhaled nitric oxide in seasonal allergic rhinitis: influence of pollen season and therapy.	2001 Mar	11260152
Effect of budesonide and nedocromil sodium on IL-6 and IL-8 release from human nasal mucosa and polyp epithelial cells.	2001 May	11392584
Budesonide but not nedocromil sodium reduces exhaled nitric oxide levels in asthmatic children.	2001 Sep	11575894
[The effect of triamcinolone acetonide, montelukast, nedocromil sodium, formoterol on levels levels of sICAM-1, sIL-2R in serum and clinical course of asthma in children].	2002 Feb	11995262
Mast cell dynamics and involvement in the development of peritoneal adhesions in the rat.	2002 Jan 11	11853232
[Exhaled nitric oxide in healthy and asthmatic children].	2002 Jul	12139887
Nedocromil sodium and levocabastine.	2002 Jul	12044267
Comparison of emedastine 0.05% or nedocromil sodium 2% eye drops and placebo in controlling local reactions in subjects with allergic conjunctivitis.	2002 Jul-Aug	12219994
Furosemide: progress in understanding its diuretic, anti-inflammatory, and bronchodilating mechanism of action, and use in the treatment of respiratory tract diseases.	2002 Jul-Aug	12115021
Mast cells involvement in the inflammation and fibrosis development of the TNBS-induced rat model of colitis.	2002 Mar	11916196
Asthma: knowledge and practice patterns of Louisiana family physicians.	2002 May-Jun	12139358
Human ocular mast cells.	2002 Oct	12582326
Corneal flap complications in refractive surgery: Part 2: postoperative treatments of diffuse lamellar keratitis in an experimental animal model.	2003 Apr	12686253
Immune response to hepatitis B vaccine in asthmatic children.	2003 Dec	14618645
A review of once-daily delivery of anti-asthmatic drugs in children.	2003 Feb	12603705
Limitations of maintenance therapy for viral respiratory infection-induced asthma.	2003 Feb	12584516
Two mast cell stabilizers, pemirolast potassium 0.1% and nedocromil sodium 2%, in the treatment of seasonal allergic conjunctivitis: a comparative study.	2003 Jan-Feb	12772816
Asthma and other wheezing disorders of childhood.	2003 Jun	15366138
Treatment compliance, passive smoking, and asthma control: a three year cohort study.	2003 Mar	12598385
Arterial hypoxemia in exercising thoroughbreds is not affected by pre-exercise nedocromil sodium inhalation.	2003 Mar 3	12609481
Single-dose agents in the prevention of exercise-induced asthma: a descriptive review.	2004	15658883
Inhaled cromones for prolonged non-specific cough in children.	2004	15106252
Comparative effect of triamcinolone, nedocromil and montelukast on asthma control in children: A randomized pragmatic study.	2004 Aug	15305946
Evidence-based asthma management.	2004 Jul	15222910
Disodium cromoglycate suppresses the induction of cysteinyl leukotriene synthesis during granulocytic differentiation in HL-60 cells.	2004 Mar	15002759
Clinical inquiries. Is nedocromil effective in preventing asthmatic attacks in patients with asthma?	2004 Nov	15527735
Safety and application of induced sputum analysis in childhood asthma.	2004 Sep	15356559
Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis.	2005	15631542
Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma.	2005 Jun 3	15935090
Childhood asthma: treatment update.	2005 May 15	15926412

Patents

Sample Use Guides

In Vivo Use Guide

Instill 1-2 gtt in each eye twice daily throughout time of exposure (ie, until pollen season is over or offending allergen terminated)

Route of Administration: Topical

In Vitro Use Guide

Eosinophil chemotaxis was studied using a modified Boyden chamber technique. Sets of six chambers each were set up to investigate different experimental conditions. Half a millilitre of either medium 199, conditioned medium, or conditioned medium containing 10^-7, 10^-6 or 10^-5 M nedocromil sodium, was placed in the lower compartment of each chamber, and incubated for 90 min at 37°C in the presence of 2510^3 eosinophils in the upper compartment, separated by an 8 m pore size microporous polycarbonate membrane. At the end of incubation, the membrane was removed, fixed in absolute alcohol for 5 min and then washed under running tap water for 1 min. The membrane was stained with Chromotrope R for 5 min. The stained membrane was dehydrated in absolute alcohol for 5 min, cleared in CNP 30 reagent (BDH LaboratorySupplies, Lutterworth, UK), and then mounted in Styrolite™ mounting medium. The membrane was immediately examined by light microscopy, and the number of eosinophils coming through to the other side of the membrane was counted in 10 random high power fields (HPF) at x40 magnification.

Name

Type

Language

NEDOCROMIL CALCIUM

Official Name

English

4H-PYRANO(3,2-G)QUINOLINE-2,8-DICARBOXYLIC ACID, 9-ETHYL-6,9-DIHYDRO-4,6-DIOXO-10-PROPYL-, CALCIUM SALT (1:1)

Common Name

English

FPL-59002KC

Code

English

FPL 59002KC

Code

English

Calcium 9-ethyl-6,9-dihydro-4,6-dioxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate (1:1)

Systematic Name

English

Nedocromil calcium [WHO-DD]

Common Name

English

NEDOCROMIL CALCIUM [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C257