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

Molecular Formula	C19H15NO7
Molecular Weight	369.3249
Charge	-2
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	Ca
Molecular Weight	40.078
Charge	2
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
Effects of nedocromil sodium and WEB 2086 on chemoattractant-stimulated neutrophil migration through cellular and noncellular barriers.	1992 Oct	1329582
Choosing therapy for childhood asthma.	2001	11772152
Inhaled hyperosmolar agents for bronchiectasis.	2001	11406058
Fog-induced respiratory responses are attenuated by nedocromil sodium in humans.	2001 Apr	11316646
Management of asthma in children.	2001 Apr 1	11310649
Inhaled nedocromil sodium for persistent cough in children.	2001 Dec	12014758
Is budesonide or nedocromil superior in the long-term management of mild to moderate asthma in children?	2001 Jan	11195486
Double-blind, randomized, placebo-controlled trial of effect of nedocromil sodium on clinical and inflammatory parameters of asthma in children allergic to dust mite.	2001 Jun	11421896
Asthma in the hospitalized obstetrical patient.	2001 Jun	11413902
[Anti-allergy therapy in children].	2001 Mar	11386127
A retrospective study of risk factors for repeated admissions for asthma in a rural/suburban university hospital.	2001 May	11409260
Effect of budesonide and nedocromil sodium on IL-6 and IL-8 release from human nasal mucosa and polyp epithelial cells.	2001 May	11392584
[IL-10 serum levels in children with moderate asthma].	2002	12148173
Montelukast: a review of its therapeutic potential in asthma in children 2 to 14 years of age.	2002	11888359
Inhaled hyperosmolar agents for bronchiectasis.	2002	11869647
24-hour efficacy of once-daily desloratadine therapy in patients with seasonal allergic rhinitis [ISRCTN32042139].	2002 Aug 5	12162793
Using case management to increase antiinflammatory medication use among a managed care population with asthma.	2002 Feb	11883740
Mast cell dynamics and involvement in the development of peritoneal adhesions in the rat.	2002 Jan 11	11853232
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
Human ocular mast cells.	2002 Oct	12582326
Respiratory function changes in a wilderness multisport endurance competition: a prospective case study.	2002 Summer	12092967
Allergen challenge and deposition of nedocromil sodium in asthma.	2002 Winter	12581508
Antiasthmatic effects of nedocromil sodium.	2003	15168867
Minimizing attrition in a long-term clinical trial of pediatric asthma.	2003 Aug	12952111
A placebo-controlled comparison of ketotifen fumarate and nedocromil sodium ophthalmic solutions for the prevention of ocular itching with the conjunctival allergen challenge model.	2003 Jul	12946546
Asthma and other wheezing disorders of childhood.	2003 Jun	15366138
Long-term safety of fluticasone propionate and nedocromil sodium on bone in children with asthma.	2003 Jun	12777589
Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma.	2003 May	12756375
Inhaled cromones for prolonged non-specific cough in children.	2004	15106252
Topical treatments for seasonal allergic conjunctivitis: systematic review and meta-analysis of efficacy and effectiveness.	2004 Jun	15186569
Investigation into the mechanisms by which nedocromil sodium, frusemide and bumetanide inhibit the histamine-induced itch and flare response in human skin in vivo.	2004 Mar	15005740
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
Respiratory morbidity in office workers in a water-damaged building.	2005 Apr	15811840

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:52:14 GMT 2023` Edited by `admin` on `Fri Dec 15 15:52:14 GMT 2023`
Record UNII	0983W479HH
Record Status	`Validated (UNII)`
Record Version

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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