OXATOMIDE MONOHYDRATE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H30N4O.H2O
Molecular Weight	444.5686
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O=C1NC2=C(C=CC=C2)N1CCCN3CCN(CC3)C(C4=CC=CC=C4)C5=CC=CC=C5

InChI

InChIKey=WUVRHFANMRXNRX-UHFFFAOYSA-N

InChI=1S/C27H30N4O.H2O/c32-27-28-24-14-7-8-15-25(24)31(27)17-9-16-29-18-20-30(21-19-29)26(22-10-3-1-4-11-22)23-12-5-2-6-13-23;/h1-8,10-15,26H,9,16-21H2,(H,28,32);1H2

HIDE SMILES / InChI

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/24474428
Curator's Comment: description was created based on several sources, including, http://www.hindawi.com/journals/jphar/2013/629593/

Oxatomide is a H1-histamine receptor antagonist developed for the treatment of broad spectrum of allergic and other hypersensitivity reactions. The drug is currently marketed in Japan, Taiwan, Italy, Portugal, Indonesia, Argentina, South Africa.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 316 Target ID: P35367 Gene ID: 3269.0 Gene Symbol: HRH1 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/8753840	Antagonist 2849		6.23 null [pIC50]

Conditions

Condition	Modality	Highest Phase	Product
Chronic urticaria 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7014277	Primary	Approved 8583	TINSET Approved Use Prevention and treatment of allergic diseases: rhinitis, extrinsic asthma (excluding asthma attacks), follicular conjunctivitis, chronic urticaria, atopic dermatitis, food allergies. Launch Date 2014
Follicular conjunctivitis 2 Sources: https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_000045_025293_RCP.pdf&retry=0&sys=m0b1l3	Primary	Approved 8583	TINSET Approved Use Prevention and treatment of allergic diseases: rhinitis, extrinsic asthma (excluding asthma attacks), follicular conjunctivitis, chronic urticaria, atopic dermatitis, food allergies. Launch Date 2014
Asthma 244 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12804426	Palliative	Approved 8583	TINSET Approved Use Prevention and treatment of allergic diseases: rhinitis, extrinsic asthma (excluding asthma attacks), follicular conjunctivitis, chronic urticaria, atopic dermatitis, food allergies. Launch Date 2014
Perennial allergic rhinitis 47 Sources: http://www.ncbi.nlm.nih.gov/pubmed/1982723	Primary	Approved 8583	TINSET Approved Use Prevention and treatment of allergic diseases: rhinitis, extrinsic asthma (excluding asthma attacks), follicular conjunctivitis, chronic urticaria, atopic dermatitis, food allergies. Launch Date 2014
Atopic eczema 2 Sources: https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_000045_025293_RCP.pdf&retry=0&sys=m0b1l3	Primary	Approved 8583	TINSET Approved Use Prevention and treatment of allergic diseases: rhinitis, extrinsic asthma (excluding asthma attacks), follicular conjunctivitis, chronic urticaria, atopic dermatitis, food allergies. Launch Date 2014
Food allergy 2 Sources: https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_000045_025293_RCP.pdf&retry=0&sys=m0b1l3	Primary	Approved 8583	TINSET Approved Use Prevention and treatment of allergic diseases: rhinitis, extrinsic asthma (excluding asthma attacks), follicular conjunctivitis, chronic urticaria, atopic dermatitis, food allergies. Launch Date 2014

C_max

Value	Dose	Co-administered	Analyte	Population
13.6 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_4490005F1603_1_071_1F.pdf#paage=19	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		OXATOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13.2 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_4490005F1603_1_071_1F.pdf#paage=20	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		OXATOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
84.6 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_4490005F1603_1_071_1F.pdf#paage=19	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		OXATOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
92.1 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_4490005F1603_1_071_1F.pdf#paage=20	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		OXATOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.6 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_4490005F1603_1_071_1F.pdf#paage=19	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		OXATOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.3 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/300119_4490005F1603_1_071_1F.pdf#paage=20	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		OXATOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.3% OTHER GOV'T https://www.info.pmda.go.jp/go/interview/2/331552_4490005F1433_2_005_1F.pdf#page=17			OXATOMIDE serum	Homo sapiens

Doses

Dose	Population	Adverse events
30 mg 2 times / day multiple, oral Recommended Dose: 30 mg, 2 times / day Route: oral Route: multiple Dose: 30 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6151914/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6151914/	Other AEs: Somnolence, Cramps... Other AEs: Somnolence (5.3%) Cramps (5.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/6151914/
30 mg 3 times / day multiple, oral Recommended Dose: 30 mg, 3 times / day Route: oral Route: multiple Dose: 30 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6119170/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6119170/	Sources: https://pubmed.ncbi.nlm.nih.gov/6119170/
1 mg/kg 2 times / day multiple, oral Recommended Dose: 1 mg/kg, 2 times / day Route: oral Route: multiple Dose: 1 mg/kg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6986007/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6986007/	Sources: https://pubmed.ncbi.nlm.nih.gov/6986007/

AEs

AE	Significance	Dose	Population
Cramps	5.3%	30 mg 2 times / day multiple, oral Recommended Dose: 30 mg, 2 times / day Route: oral Route: multiple Dose: 30 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6151914/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6151914/
Somnolence	5.3%	30 mg 2 times / day multiple, oral Recommended Dose: 30 mg, 2 times / day Route: oral Route: multiple Dose: 30 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6151914/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6151914/

PubMed

Title	Date	PubMed
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011-07-14	21599003
An integrative review of systematic reviews related to the management of breathlessness in respiratory illnesses.	2010-12-09	21143887
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010-12	21818443
Treatment of allergic rhinitis in infants and children: efficacy and safety of second-generation antihistamines and the leukotriene receptor antagonist montelukast.	2009	19943707
Determination of oxatomide in human plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry.	2008-07	18348338
Intact cell binding for in vitro prediction of sedative and non-sedative histamine H1-receptor antagonists based on receptor internalization.	2008-05	18446005
Inhibition of angiogenic factor production from murine mast cells by an antiallergic agent (epinastine hydrochloride) in vitro.	2008	18725994
CINRG pilot trial of oxatomide in steroid-naïve Duchenne muscular dystrophy.	2007-11	17459739
A simple preparation method for mouse eosinophils and their responses to anti-allergic drugs.	2007-03	17406808
Solvent effect on the charge transfer complex of oxatomide with 2,3-dichloro-5,6-dicyanobenzoquinone.	2006-12	16488184
Effect of inhibitor of tumor necrosis factor-alpha and oxatomide on immune mediated otitis media.	2006-09	16954996
Severe cholinergic urticaria successfully treated with scopolamine butylbromide in addition to antihistamines.	2006-07	16716168
[Comparison of clinical efficacy and cost-quality of antihistamines in early treatment for Japanese cedar pollinosis].	2006-05	16883093
Nimesulide-induced fixed drug eruption.	2005-11-17	16287549
Antipruritic effect of the single oral administration of German chamomile flower extract and its combined effect with antiallergic agents in ddY mice.	2005-10-03	15964726
Hydroxyzine and metabolites as a source of interference in carbamazepine particle-enhanced turbidimetric inhibition immunoassay (PETINIA).	2005-08	16044102
Identification of human P450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its kinetic parameters and inhibition constants.	2005-02	15684493
The measurement of health-related quality of life (QOL) in paediatric clinical trials: a systematic review.	2004-11-22	15555077
Identification of human p450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its inhibitory effect on enzyme activity.	2004-05	15133245
West syndrome associated with administration of a histamine H1 antagonist, oxatomide.	2004	15682834
Cetirizine: a review of its use in allergic disorders.	2004	14977391
Dietary intake of the flower extracts of German chamomile (Matricaria recutita L.) inhibited compound 48/80-induced itch-scratch responses in mice.	2003-11	14692726
[Development of nasal dosage form of oxatomide for rhinitis].	2003-10	14685044
Effects of fexofenadine and other antihistamines on components of the allergic response: adhesion molecules.	2003-10	14530792
Enhancement of allergic skin wheal responses in patients with atopic eczema/dermatitis syndrome by playing video games or by a frequently ringing mobile phone.	2003-06	12795649
Evaluation of the effects of anti-pruritic drugs on scratch responses using histamine H1 receptor-deficient mice.	2003-05-30	12787839
The antiallergic drug oxatomide promotes human eosinophil apoptosis and suppresses IL-5-induced eosinophil survival.	2003-03	12642838
Oxatomide for stable asthma in adults and children.	2003	12804426
Pranlukast: a review of its use in the management of asthma.	2003	12699401
The comparison of the efficacy and safety of cetirizine, oxatomide, ketotifen, and a placebo for the treatment of childhood perennial allergic rhinitis.	2002-12	12487225
Drug eruption and liver injury caused by terfenadine and oxatomide.	2002-07-04	12095890
Gateways to clinical trials.	2002-05-01	11980386
Pharmacokinetics of oxatomide in preterm infants.	2002	12635496
High-performance liquid chromatographic determination of oxatomide and its metabolite and its application to pharmacokinetic study in rat plasma.	2002	12442638
The role of central histaminergic neuron system as an anticonvulsive mechanism in developing brain.	2001-11	11701252
Preclinical comparison of ebastine and other second generation H1-antihistamines.	2001-10	11881966
Circumvention of acquired resistance to doxorubicin in K562 human leukemia cells by oxatomide.	2001-10	11642329
Oxatomide in the treatment of atopic dermatitis in breast-fed and very young infants.	2001-08	11573062
Double-blind multicenter study on the efficacy and tolerability of cetirizine compared with oxatomide in chronic idiopathic urticaria in preschool children.	2001-07	11476462
Change in tissue kallikrein level in nasal wash after the administration of oxatomide in patients with nasal allergy.	2001-05-10	11345148
Effect of oxatomide, an antiallergic agent, on QT interval in dogs.	2001	11799844
Inhibition of mediator release in RBL-2H3 cells by some H1-antagonist derived anti-allergic drugs: relation to lipophilicity and membrane effects.	1995-02	7655991

Patents

Sample Use Guides

In Vivo Use Guide

Oxatomide should be taken twice daily, after breakfast and after dinner: 30 mg for adults and 0.5 mg/kg for children older tan 1 year.

Route of Administration: Oral

In Vitro Use Guide

The effect of oxatomide on the immunologic release of preformed (histamine and tryptase) and de novo synthesized mediators (leukotriene C4:LTC4 and prostaglandin D2:PGD2) from human basophils and mast cells purified (from 10 to 82%) from human lung parenchyma (HLMC) and skin tissue (HSMC) was studied in vitro. Preincubation (15 min, 37 degrees C) of basophils with oxatomide (10(-7)-10(-5) M) before Der p I antigen or anti-IgE challenge concentration-dependently (10-40%) inhibited the immunologic release of histamine and LTC4. Oxatomide (10(-7)-10(-5) M) also inhibited (10-40%) histamine, tryptase and LTC4 release from HLMC activated by anti-IgE. In addition, oxatomide caused a concentration-dependent inhibition of histamine, tryptase and PGD2 release from HSMC immunologically challenged with a monoclonal antibody against the alpha chain of the high affinity receptor for IgE (anti-Fc epsilon RI) or anti-IgE.

Name

Type

Language

2H-BENZIMIDAZOL-2-ONE, 1-(3-(4-(DIPHENYLMETHYL)-1-PIPERAZINYL)PROPYL)-1,3-DIHYDRO-, HYDRATE (1:1)

Preferred Name

English

OXATOMIDE MONOHYDRATE

Common Name

English

2H-BENZIMIDAZOL-2-ONE, 1-(3-(4-(DIPHENYLMETHYL)-1-PIPERAZINYL)PROPYL)-1,3-DIHYDRO-, MONOHYDRATE

Systematic Name

English

Code System Code Type Description

SMS_ID

100000130699