DAPSONE

First approved in 1955

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H12N2O2S
Molecular Weight	248.3024
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1cc(ccc1N)S(=O)(=O)c2ccc(cc2)N

InChI

InChIKey=MQJKPEGWNLWLTK-UHFFFAOYSA-N

InChI=1S/C12H12N2O2S/c13-9-1-5-11(6-2-9)17(15,16)12-7-3-10(14)4-8-12/h1-8H,13-14H2

HIDE SMILES / InChI

Description
Sources: http://escholarship.org/uc/item/30m4b5kr
Curator's Comment:: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021794s000_MicroR.pdf

Dapsone was synthesized in 1908 by Fromm and Wittmann. The drug was approved by FDA for the treatment of such conditions as acne vulgaris, leprosy and dermatitis herpetiformis, also the drug is used off-label for many skin diseases. Although the exact mechanism of dapsone action is unknown, it is speculated that it acts as both anti-inflammatory and antimicrobial agent. It was demonstrated that dapsone suppresses ROS generation, inhibits neutrophil myeloperoxidase and eosinophil peroxidase and also inhibits bacterial dihydropteroate synthase.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial dihydropteroate synthase 42 Target ID: CHEMBL2364668 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24310318	Inhibitor 7728

Conditions

Condition	Modality	Highest Phase	Product
Acne vulgaris 30 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021794s013lbl.pdf	Curative	Approved 8043	ACZONE Approved Use Gel is indicated for the topical treatment of acne vulgaris. Launch Date -4.73385599E11
Dermatitis herpetiformis 9 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7fc98c9b-b17a-f66f-055b-259207ad9504	Curative	Approved 8043	DAPSONE Approved Use Dermatitis herpetiformis: (D.H.) Leprosy: All forms of leprosy except for cases of proven Dapsone resistance. Launch Date 2.99807998E11
Leprosy 5 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7fc98c9b-b17a-f66f-055b-259207ad9504	Curative	Approved 8043	DAPSONE Approved Use Dermatitis herpetiformis: (D.H.) Leprosy: All forms of leprosy except for cases of proven Dapsone resistance. Launch Date 2.99807998E11

C_max

Value	Dose	Co-administered	Analyte	Population
1375 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		DAPSONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	110 mg 2 times / day steady-state, topical dose: 110 mg route of administration: Topical experiment type: STEADY-STATE co-administered:		DAPSONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
221.52 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	110 mg 2 times / day steady-state, topical dose: 110 mg route of administration: Topical experiment type: STEADY-STATE co-administered:	DAPSONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22783 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	DAPSONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
415 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	110 mg 2 times / day steady-state, topical dose: 110 mg route of administration: Topical experiment type: STEADY-STATE co-administered:	DAPSONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
52641 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	DAPSONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
20.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		DAPSONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	110 mg 2 times / day steady-state, topical dose: 110 mg route of administration: Topical experiment type: STEADY-STATE co-administered:		DAPSONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% REVIEW https://pubmed.ncbi.nlm.nih.gov/3530584	unknown, unknown		DAPSONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 1 times / week multiple, oral Highest studied dose Dose: 300 mg, 1 times / week Route: oral Route: multiple Dose: 300 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582	unhealthy, 38 n = 9 Health Status: unhealthy Condition: Pneumocystis pneumonia Age Group: 38 Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582	Disc. AE: Anemia, Rash... AEs leading to discontinuation/dose reduction: Anemia (11.1%) Rash (11.1%) Fever (11.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582
200 mg 1 times / week multiple, oral MTD Dose: 200 mg, 1 times / week Route: oral Route: multiple Dose: 200 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582	unhealthy, 38 n = 7 Health Status: unhealthy Condition: Pneumocystis pneumonia Age Group: 38 Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582	Disc. AE: Vomiting, Fever... AEs leading to discontinuation/dose reduction: Vomiting (14.3%) Fever (14.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582
10 g single, oral Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Sources: https://pubmed.ncbi.nlm.nih.gov/6660028 Page: p.216	unhealthy, 45 n = 1 Health Status: unhealthy Condition: Dermatitis herpatiformis Age Group: 45 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6660028 Page: p.216	Disc. AE: Cyanosis, Methaemoglobinaemia... AEs leading to discontinuation/dose reduction: Cyanosis (acute) Methaemoglobinaemia Haemolysis Sources: https://pubmed.ncbi.nlm.nih.gov/6660028 Page: p.216

AEs

AE	Significance	Dose	Population
Anemia	11.1% Disc. AE	300 mg 1 times / week multiple, oral Highest studied dose Dose: 300 mg, 1 times / week Route: oral Route: multiple Dose: 300 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582	unhealthy, 38 n = 9 Health Status: unhealthy Condition: Pneumocystis pneumonia Age Group: 38 Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582
Fever	11.1% Disc. AE	300 mg 1 times / week multiple, oral Highest studied dose Dose: 300 mg, 1 times / week Route: oral Route: multiple Dose: 300 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582	unhealthy, 38 n = 9 Health Status: unhealthy Condition: Pneumocystis pneumonia Age Group: 38 Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582
Rash	11.1% Disc. AE	300 mg 1 times / week multiple, oral Highest studied dose Dose: 300 mg, 1 times / week Route: oral Route: multiple Dose: 300 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582	unhealthy, 38 n = 9 Health Status: unhealthy Condition: Pneumocystis pneumonia Age Group: 38 Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582
Fever	14.3% Disc. AE	200 mg 1 times / week multiple, oral MTD Dose: 200 mg, 1 times / week Route: oral Route: multiple Dose: 200 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582	unhealthy, 38 n = 7 Health Status: unhealthy Condition: Pneumocystis pneumonia Age Group: 38 Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582
Vomiting	14.3% Disc. AE	200 mg 1 times / week multiple, oral MTD Dose: 200 mg, 1 times / week Route: oral Route: multiple Dose: 200 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582	unhealthy, 38 n = 7 Health Status: unhealthy Condition: Pneumocystis pneumonia Age Group: 38 Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/7979291 Page: p.1582
Haemolysis	Disc. AE	10 g single, oral Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Sources: https://pubmed.ncbi.nlm.nih.gov/6660028 Page: p.216	unhealthy, 45 n = 1 Health Status: unhealthy Condition: Dermatitis herpatiformis Age Group: 45 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6660028 Page: p.216
Methaemoglobinaemia	Disc. AE	10 g single, oral Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Sources: https://pubmed.ncbi.nlm.nih.gov/6660028 Page: p.216	unhealthy, 45 n = 1 Health Status: unhealthy Condition: Dermatitis herpatiformis Age Group: 45 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6660028 Page: p.216
Cyanosis	acute Disc. AE	10 g single, oral Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Sources: https://pubmed.ncbi.nlm.nih.gov/6660028 Page: p.216	unhealthy, 45 n = 1 Health Status: unhealthy Condition: Dermatitis herpatiformis Age Group: 45 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6660028 Page: p.216

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1601	substrate 936 activator 20

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C8 634 CYP2E1 606

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C9 1648	activator 202 Sources: https://pubmed.ncbi.nlm.nih.gov/11408370/	likely

Drug as victim

Target	Modality	Activity
CYP2C8 634	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19998329/	yes
CYP2C9 936	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19998329/	yes
CYP2E1 606	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19998329/	yes
CYP3A4 1601	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/19998329/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4325	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4325
ChemicalBook	CB0152851	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0152851
MolPort	MolPort-001-780-172	https://www.molport.com/shop/molecule-link/MolPort-001-780-172
ZINC	ZINC000000006310	http://zinc15.docking.org/substances/ZINC000000006310
eMolecules	17392619	https://www.emolecules.com/cgi-bin/more?vid=17392619
eMolecules	498059	https://www.emolecules.com/cgi-bin/more?vid=498059

PubMed

Title	Date	PubMed
Evaluation of the sulfones and streptomycin in experimental tuberculosis.	1949 Dec 14	15398779
Dapsone-induced motor polyneuropathy. A complication of prolonged treatment of subcorneal pustular dermatosis.	1976 Aug	182085
Dapsone-induced peripheral neuropathy.	1976 Dec	188385
[Polyneuropathy in Duhring dermatitis herpetiformis].	1991 Aug	1944718
[Granulomatous hepatitis caused by dapsone].	1992	1582552
Dapsone suppresses integrin-mediated neutrophil adherence function.	1992 Feb	1732379
A case of refractory bullous pemphigoid with plasmapheresis-associated thrombopenia: efficacy of pulsed intravenous cyclophosphamide therapy.	2004 Aug	15492438
Young children's sensitivity to probabilistic phonotactics in the developing lexicon.	2004 Nov	15501451
Simultaneous determination of beta-blocking agents and diuretics in doping analysis by liquid chromatography/mass spectrometry with scan-to-scan polarity switching.	2005	15584083
Dapsone syndrome with acute renal failure during leprosy treatment: case report.	2005 Feb	15947852
Relationships between nonword repetition accuracy and other measures of linguistic development in children with phonological disorders.	2005 Feb	15938060
[Dapsone-induced agranulocytosis. The role of xenobiotic-metabolizing enzymes demonstrated by a case report].	2005 Jul	15999287
Dapsone impairs the bile salt-independent fraction of bile flow in rats: Possible involvement of its N-hydroxylated metabolite.	2005 Jul 1	15863252
Aplastic anaemia associated with multidrug therapy (dapsone, rifampicin and clofazimine) in a patient with lepromatous leprosy.	2005 Jun	16038251
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Dapsone suppresses human neutrophil superoxide production and elastase release in a calcium-dependent manner.	2005 May	15888142
Differential antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates.	2005 Nov	16251329
Complications related to dapsone use for Pneumocystis jirovecii pneumonia prophylaxis in solid organ transplant recipients.	2005 Nov	16212642
Childhood bullous pemphigoid successfully treated with diaminodiphenyl sulfone.	2005 Oct	16361732
A case of drug-induced hypersensitivity syndrome with multiple organ involvement treated with plasma exchange.	2005 Oct	16202017
Renal hypersensitivity vasculitis associated with dapsone.	2005 Oct	16183407
Protective role of vitamin E on the oxidative stress in Hansen's disease (Leprosy) patients.	2005 Oct	16015260
The contribution of prosody to the perception of foreign accent.	2006	17293645
Acute methemoglobinemia following attempted suicide by Dapson.	2006 Apr	16513495
Anterior ischaemic optic neuropathy associated with Dapsone.	2006 Aug	16215545
[Disulone and hepatosiderosis].	2006 Aug-Sep	17053738
Guillain-Barré syndrome-like presentation in borderline leprosy with type-2 reaction.	2006 Feb 28	16638414
Role of human cyclooxygenase-2 in the bioactivation of dapsone and sulfamethoxazole.	2006 Jan	16214851
[Refractory cutaneous necrotizing vasculitis. Successful sulfone therapy].	2006 Jan	15662534
The Dapsone hypersensitivity syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations.	2006 Jun 6	16756657
The sulfone syndrome secondary to dapsone prophylaxis in a patient undergoing unrelated hematopoietic stem cell transplantation.	2006 Sep	16639690
Neuroprotective effect of dapsone in patients with acute ischemic stroke: a pilot study.	2007 Apr	17509235
Consultative meeting to develop a strategy for treatment of cutaneous leishmaniasis. Institute Pasteur, Paris. 13-15 June, 2006.	2007 Apr 24	17456237
Anti-inflammatory and immune therapy for Alzheimer's disease: current status and future directions.	2007 Dec	19305740
[Long-term follow-up of ofloxacin-combined therapy for leprosy patients].	2007 Sep	17877033
High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency.	2008	19112496
Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver.	2008 Aug 1	18602405
Dapsone-induced haemolytic anaemia, hepatitis and agranulocytosis in a leprosy patient with normal glucose-6-phosphate-dehydrogenase activity.	2008 Dec	19274991
Beneficial effects of word final stress in segmenting a new language: evidence from ERPs.	2008 Feb 18	18282274
[A case of relapsing polychondritis monitored by repeated measurements of flow-volume curve].	2008 Mar	18409570
Open-label comparative clinical study of chlorproguanil-dapsone fixed dose combination (Lapdap) alone or with three different doses of artesunate for uncomplicated Plasmodium falciparum malaria.	2008 Mar 5	18320064
A novel assay system for myeloperoxidase activity in whole saliva.	2008 May	18237554
Dapsone-induced hemolytic anemia in lung allograft recipients.	2008 Nov	18971091
A possible inhibitory action of diaminodiphenyl sulfone on tumour necrosis factor-alpha production from activated mononuclear cells on cutaneous lupus erythematosus.	2008 Nov	18713254
Antioxidant, antiinflammatory and antiapoptotic effects of dapsone in a model of brain ischemia/reperfusion in rats.	2008 Nov 15	18615706
The processing of English regular inflections: Phonological cues to morphological structure.	2008 Oct	18834584
Complex phase separation in poly(acrylonitrile-butadiene-styrene)-modified epoxy/4,4'-diaminodiphenyl sulfone blends: generation of new micro- and nanosubstructures.	2009 Apr 23	19331324
Complete atrioventricular block associated with dapsone therapy: a rare complication of dapsone-induced hypersensitivity syndrome.	2009 Aug	19583683
Representation of time-varying stimuli by a network exhibiting oscillations on a faster time scale.	2009 May	19412531
Establishment of knockdown of superoxide dismutase 2 and expression of CYP3A4 cell system to evaluate drug-induced cytotoxicity.	2009 Sep	19501153

Patents

Sample Use Guides

In Vivo Use Guide

Apply 5% gel to the acne affected areas twice a day (Aczone gel). In dermatitis herpetiformis, the starting oral dose is 50 mg and in leprosy, the dose is 100 mg/day (Dapsone oral formulation).

Route of Administration: Other

In Vitro Use Guide

With Staphylococcus aureus (both methicillin-susceptible S. aureus-MSSA and methicillinresistant S. aureus-MRSA), dapsone MIC50, MIC90 were 128 ug/mL and 256 ug/mL, respectively. For Staphylococcus epidermidis overall, dapsone MIC50, MIC90 were 128 ug/mL and 256 ug/mL, respectively. Overall results with Enterococcus faecalis, dapsone MIC50, MIC90 were 256 ug/mL and 512 ug/mL, respectively. With Streptococcus agalactiae, dapsone MIC50, MIC90 were reported overall to be 32 ug/mL and 256 ug/mL, respectively. For Streptococcus pyogenes, dapsone MIC50, MIC90 were 32 ug/mL and 512 ug/mL, respectively.

Name

Type

Language

DAPSONE

Official Name

English

DAPSONE [VANDF]

Common Name

English

ACZONE

Brand Name

English

DAPSONE [WHO-IP]

Common Name

English

NSC-6091

Code

English

DAPSONE [INN]

Common Name

English

SULFACETAMIDE SODIUM IMPURITY D [EP]

Common Name

English

4,4'-SULFONYLDIANILINE

Systematic Name

English

DAPSONE [USP MONOGRAPH]

Common Name

English

DAPSONE [HSDB]

Common Name

English

DAPSONE [EP MONOGRAPH]

Common Name

English

DAPSONE [MART.]

Common Name

English

NOVOPHONE

Common Name

English

DAPSONUM [WHO-IP LATIN]

Common Name

English

DAPSONE [EP]

Common Name

English

DAPSONE [IARC]

Common Name

English

J04BA02

Code

English

DIAPHENYLSULFONE [JAN]

Common Name

English

DIAPHENYLSULFONE

Common Name

English

BENZENAMINE, 4,4'-SULFONYLBIS-

Systematic Name

English

DAPSONE [ORANGE BOOK]

Common Name

English

DAPSONE [WHO-DD]

Common Name

English

DAPSONE [MI]

Common Name

English

DAPSONE [USP-RS]

Common Name

English

NSC-6091D

Code

English

DAPSONE [USAN]

Common Name

English

SERVIDAPSON

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000008053