DIETHYLCARBAMAZINE CITRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H21N3O.C6H8O7
Molecular Weight	391.4168
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC(O)(CC(O)=O)C(O)=O.CCN(CC)C(=O)N1CCN(C)CC1

InChI

InChIKey=PGNKBEARDDELNB-UHFFFAOYSA-N

InChI=1S/C10H21N3O.C6H8O7/c1-4-12(5-2)10(14)13-8-6-11(3)7-9-13;7-3(8)1-6(13,5(11)12)2-4(9)10/h4-9H2,1-3H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)

HIDE SMILES / InChI

Description
Sources: http://apps.who.int/medicinedocs/en/d/Jh2922e/3.5.1.html
Curator's Comment: description was created based on several sources, including http://filobase.bicpu.edu.in/banocide.pdf

Diethylcarbamazine is used in humans, dogs and cats for the treatment of parasitic infections, including pulmonary eosinophilia, loiasis, and lymphatic filariasis. The exact mechanism of its action is unknown, however some studies showed the involvment of inducible nitric-oxide synthase and the cyclooxygenase pathway. Although there is no information on whether the drug is marketed in the USA and Europe, it is currently used in India.

Approval Year

Conditions

Condition	Modality	Highest Phase	Product
Tropical pulmonary eosinophilia 3 Sources: http://india-pharma.gsk.com/media/701051/banocide-and-banocide-forte.pdf	Curative	Approved 8429	BANOCIDE Approved Use Used for the treatment of individual patients with certain filarial diseases including tropical pulmonary eosinophilia, loiasis, and lymphatic filariasis caused by infection with Wuchereria bancrofti, Brugia malayi, or Brugia timori.
Loiasis 3 Sources: http://india-pharma.gsk.com/media/701051/banocide-and-banocide-forte.pdf	Curative	Approved 8429	BANOCIDE Approved Use Used for the treatment of individual patients with certain filarial diseases including tropical pulmonary eosinophilia, loiasis, and lymphatic filariasis caused by infection with Wuchereria bancrofti, Brugia malayi, or Brugia timori.
Lymphatic filariasis 3 Sources: http://india-pharma.gsk.com/media/701051/banocide-and-banocide-forte.pdf	Curative	Approved 8429	BANOCIDE Approved Use Used for the treatment of individual patients with certain filarial diseases including tropical pulmonary eosinophilia, loiasis, and lymphatic filariasis caused by infection with Wuchereria bancrofti, Brugia malayi, or Brugia timori.

C_max

Value	Dose	Co-administered	Analyte	Population
500 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11865970/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		DIETHYLCARBAMAZINE serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
637 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11865970/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		DIETHYLCARBAMAZINE serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
5840 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11865970/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		DIETHYLCARBAMAZINE serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
7220 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11865970/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		DIETHYLCARBAMAZINE serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
14.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11865970/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		DIETHYLCARBAMAZINE serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
11.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11865970/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		DIETHYLCARBAMAZINE serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
6 mg/kg 1 times / day multiple, oral Studied dose Dose: 6 mg/kg, 1 times / day Route: oral Route: multiple Dose: 6 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7001687/	unhealthy, 12 to 69 years n = 11 Health Status: unhealthy Condition: filariasis Age Group: 12 to 69 years Sex: M+F Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/7001687/	Other AEs: Fever, Pruritus... Other AEs: Fever (63.6%) Pruritus (9.1%) Giddiness (9.1%) Joint ache (9.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/7001687/
2 mg/kg 3 times / day multiple, oral Studied dose Dose: 2 mg/kg, 3 times / day Route: oral Route: multiple Dose: 2 mg/kg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7001687/	unhealthy, 13 to 46 years n = 11 Health Status: unhealthy Condition: filariasis Age Group: 13 to 46 years Sex: M+F Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/7001687/	Other AEs: Fever, Nausea... Other AEs: Fever Nausea (27.3%) Vomiting (18.2%) Abdominal discomfort (9.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/7001687/
50 mg multiple, oral Studied dose Dose: 50 mg Route: oral Route: multiple Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6103299/	unhealthy, 37 years n = 10 Health Status: unhealthy Condition: onchocerciasis Age Group: 37 years Sex: M Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/6103299/	Other AEs: Lymphadenopathy, Papular urticarial eruption... Other AEs: Lymphadenopathy (100%) Papular urticarial eruption (30%) Proteinuria (10%) Visual field constriction (20%) Optic nerve pallor (10%) Corneal opacity (90%) Anterior uveitis (10%) Chorioretinitis (10%) Sources: https://pubmed.ncbi.nlm.nih.gov/6103299/
300 mg multiple, topical Studied dose Dose: 300 mg Route: topical Route: multiple Dose: 300 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6103299/	unhealthy, 40 years n = 10 Health Status: unhealthy Condition: onchocerciasis Age Group: 40 years Sex: M Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/6103299/	Other AEs: Lymphadenopathy, Papular urticarial eruption... Other AEs: Lymphadenopathy (100%) Papular urticarial eruption (70%) Proteinuria (30%) Visual field constriction (10%) Optic nerve pallor (20%) Corneal opacity (80%) Anterior uveitis (30%) Chorioretinitis (30%) Sources: https://pubmed.ncbi.nlm.nih.gov/6103299/
6 mg/kg 1 times / day single, oral Studied dose Dose: 6 mg/kg, 1 times / day Route: oral Route: single Dose: 6 mg/kg, 1 times / day Co-administed with:: ivermectin(200 ug/kg; single) albendazole(400 mg; single) Sources: https://pubmed.ncbi.nlm.nih.gov/31641754/	unhealthy, median age 35 years n = 43 Health Status: unhealthy Condition: Filariasis Age Group: median age 35 years Sex: M+F Population Size: 43 Sources: https://pubmed.ncbi.nlm.nih.gov/31641754/	Other AEs: Fatigue, Nausea... Other AEs: Fatigue (grade 2, 5%) Nausea (grade 2, 2%) Vomiting (grade 2, 2%) Joint pain (grade 2, 2%) Eye swelling (grade 2, 2%) Rash (grade 2, 2%) Dyspnea (grade 2, 2%) Sources: https://pubmed.ncbi.nlm.nih.gov/31641754/
8 mg/kg 3 times / day multiple, oral (mean) Studied dose Dose: 8 mg/kg, 3 times / day Route: oral Route: multiple Dose: 8 mg/kg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1463361/	unhealthy n = 972 Health Status: unhealthy Condition: filariasis Sex: M+F Population Size: 972 Sources: https://pubmed.ncbi.nlm.nih.gov/1463361/	Other AEs: Fever, Headache... Other AEs: Fever (69%) Headache (65%) Vertigo (57%) Malaise (49%) Chills (45%) Joint pain (40%) Abdominal pain (37%) Chest pain (33%) Nausea (28%) Neck pain (24%) Vomiting (16%) Muscular pain (14%) Lymph node tenderness (38%) Epididymal tenderness (34%) Nodule (15%) Tinnitus (8%) Convulsion (2%) Eruption (<1%) Shock (<1%) Sources: https://pubmed.ncbi.nlm.nih.gov/1463361/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 OATP1B1 788 OATP1B3 706	CYP1A2 1054 CYP2B6 664 P-gp 1537	CYP1A 56

Drug as perpetrator

Target	Modality	Activity
CYP2C19 1553	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDkzNyJ9fQ%3D%3D	no [Activation >10 uM]
CYP1A 121	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/12451431/	no
CYP1A2 1692	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/29/1/30.short	no
CYP2C9 1819	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/29/1/30.short	no
CYP2D6 1891	inhibitor 3277 Sources: https://link.springer.com/article/10.1007/BF00202169	no
CYP3A4 1925	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/29/1/30.short	no
OATP1B1 803	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDkzNyJ9fQ%3D%3D	yes [Inhibition 10 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDkzNyJ9fQ%3D%3D	yes [Inhibition 10 uM]
CYP2C19 1553	activator 214 Sources: https://dmd.aspetjournals.org/content/29/1/30.short	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12920490/	likely
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12920490/	likely
CYP3A4 1737	substrate 3367 Sources: http://smj.medicine.psu.ac.th/index.php/smj/article/view/950	no	no (co-administration study) Comment: Coadministration of refampicin/ketoconazole did not affect the exposure of diethylcarbamazine. Sources: http://smj.medicine.psu.ac.th/index.php/smj/article/view/950
P-gp 1537	substrate 3367 Sources: http://smj.medicine.psu.ac.th/index.php/smj/article/view/950	no	no (co-administration study) Comment: Coadministration of refampicin/ketoconazole did not affect the exposure of diethylcarbamazine. Sources: http://smj.medicine.psu.ac.th/index.php/smj/article/view/950

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY578639	https://www.001chemical.com/chem/90-89-1
3B Scientific (Wuhan) Corp	3B3-061821	http://www.3bsc.com/index/pro_info.php?id=100910
AA Blocks	AA00IFVB	http://www.aablocks.com/goods/Goods/detail?id=AA00IFVB
AEchem Scientific Corp., USA	AE028779	http://www.aechemsc.com/info_products/AE028779.php
Aaron Chemicals	AR00IGN3	http://www.aaronchem.com/90-89-1
Achemo Scientific Limited	AC-89305	http://www.achemo.com/search/?Keyword= 90-89-1
Alichem	490014501	http://www.alichem.com/en/products/90-89-1.html
Angene	AGN-PC-0JK6FF	http://www.angenechemical.com/productshow/AGN-PC-0JK6FF.html
Ark Pharm	AK158485	http://www.arkpharminc.com/products/90-89-1.html
Ark Pharma Scientific Limited	H-012789	http://www.arkpharmtech.com/product/17844.html
Aurora Fine Chemicals LLC	A13.142.491	http://online.aurorafinechemicals.com/info?ID=A13.142.491
Aurum Pharmatech LLC	NE55264	http://www.Aurumpharmatech.com/Product/ProductDetails/NE55264
BLD Pharm	BD23082	http://www.bldpharm.com/products/90-89-1.html
ChemMol	99173714	http://www.chemmol.com/chemmol/99173714.html
Chemspace	CSSB00000693863	https://chem-space.com/CSSB00000693863
Clearsynth	CS-MM-79413	https://www.clearsynth.com/en/CSMM79413.html
Debye Scientific	DB-080764	http://www.debyesci.com/cas_90-89-1.html
Finetech	FT-0624832	http://www.finetechnology-ind.com/prod/detail/pub/90-89-1.html
Frinton	FR-1031	https://www.frinton.com/search/?filtername=NN-Diethyl-4-methyl-1-piperazinecarboxamide
Lab Network	LN01325414	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01325414
Matrix Scientific	172278	https://www.matrixscientific.com/172278.html
Molcore	MC578639	https://www.molcore.com/product/90-89-1
Parchem	28724	http://www.parchem.com/chemical-supplier-distributor/Diethyl-Carbamazine-Citrate-018724.aspx
R&D Chemicals	FR-1031	http://www.rdchemicals.com/chemicals.php?mode=details&mol_id=2751
Sigma-Aldrich	PH003578_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/ph003578
Smolecule	S526027	http://www.smolecule.com/products/s526027
THE BioTek	bt-264510	https://www.thebiotek.com/product/inhibitors/bt-264510
Yuhao Chemical	XJ0184	http://www.chemyuhao.com/90-89-1.html
abcr GmbH	AB357734	http://www.abcr.com/shop/en/AB357734
eNovation Chemicals	Y0988700	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0988700
iChemical	EBD3427	http://www.ichemical.com/chemicals/cas-90-89-1
mcule	MCULE-7296820622	https://mcule.com/MCULE-7296820622/

PubMed

Title	Date	PubMed
Antituberculosis activity of certain antifungal and antihelmintic drugs.	1999	10707260
Macrofilaricides and onchocerciasis control, mathematical modelling of the prospects for elimination.	2001	11734070
Effect of drugs used for neuropathic pain management on tetrodotoxin-resistant Na(+) currents in rat sensory neurons.	2001 Jan	11135733
Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s.	2001 Jan	11124226
Relationship between microfilaria count and sensitivity of the direct smear for diagnosis of canine dirofilariosis.	2001 Jan 1	11113550
Long-term efficacy of single-dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.	2001 May-Jun	11491010
Intraoral filarial infestation: an atypical presentation.	2001 Nov	11709679
Gas chromatographic assay of diethylcarbamazine in human plasma for application to clinical pharmacokinetic studies.	2001 Nov	11516918
Efficacy of DEC against Ascaris and hookworm infections in schoolchildren.	2001 Sep	11555442
A randomized, double-blind, placebo-controlled study with diethylcarbamazine for the treatment of hydrocoele in an area of Tanzania endemic for lymphatic filariasis.	2001 Sep-Oct	11706668
[Technical measures of filariasis elimination in Tengzhou City].	2002	12568031
Detection of Onchocerca volvulus infection in low prevalence areas: a comparison of three diagnostic methods.	2002 Dec	12553573
Major progress toward eliminating lymphatic filariasis.	2002 Dec 5	12466515
Mass treatment to eliminate filariasis in Papua New Guinea.	2002 Dec 5	12466508
Mass drug administration to treat lymphatic filariasis.	2002 Jun 1	12057582
Pharmacokinetics of diethylcarbamazine after single oral dose at two different times of day in human subjects.	2002 Mar	11865970
Neoplastic change in Onchocerca volvulus and its relation to ivermectin treatment.	2002 Nov	12458827
Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells.	2002 Nov	12451431
Microfilaria in a thyroid nodule which resolved on treatment.	2002 Oct	12405321
Efficacy and sustainability of a footcare programme in preventing acute attacks of adenolymphangitis in Brugian filariasis.	2002 Sep	12225507
Ensuring supplies of quality diethylcarbamazine citrate (DEC).	2003 May	12751269

Sample Use Guides

In Vivo Use Guide

Lymphatic filariasis: 6 mg/kg daily for 12 days administered orally, preferably in divided doses after meals (W. bancrofti infection); 3-6 mg/kg daily for 6-12 days administered orally, preferably in divided doses after meals (B. malayi and B. timori infections). Tropical pulmonary eosinophilia: a dose of 8 mg/kg daily for 14 days repeated, as necessary, if symptoms return.

Route of Administration: Oral

In Vitro Use Guide

Larvae of nocturnally subperiodic Brugia malayi was inhibited under incubation with diethylcarbamazine at concentration of 10(-5) M.

Name

Type

Language

DIETHYLCARBAMAZINE CITRATE

Common Name

English

DIETHYLCARBAMAZINE CITRATE [GREEN BOOK]

Common Name

English

LOXURAN

Common Name

English

DIETHYLCARBAMAZINE CITRATE [USP IMPURITY]

Common Name

English

1-PIPERAZINECARBOXAMIDE, N,N-DIETHYL-4-METHYL-, 2-HYDROXY-1,2,3-PROPANETRICARBOXYLATE

Systematic Name

English

DIETHYLCARBAMAZINI DIHYDROGENOCITRAS [WHO-IP LATIN]

Common Name

English

NSC-80513

Code

English

DIETHYLCARBAMAZINE CITRATE [USP-RS]

Common Name

English

Diethylcarbamazine citrate [WHO-DD]

Common Name

English

DIETHYLCARBAMAZINE CITRATE [MART.]

Common Name

English

DIETHYLCARBAMAZINE CITRATE [JAN]

Common Name

English

HETRAZAN

Brand Name

English

DIETHYLCARBAMAZINE DIHYDROGEN CITRATE [WHO-IP]

Common Name

English

DIETHYLCARBAMAZINE CITRATE [ORANGE BOOK]

Common Name

English

DIETHYLCARBAMAZINE CITRATE [MI]

Common Name

English

DIETHYLCARBAMAZINE CITRATE [HSDB]

Common Name

English

ETHYLAMINOAZINE CITRATE

Common Name

English

DIETHYLCARBAMAZINE CITRATE [USP MONOGRAPH]

Common Name

English

N,N-Diethyl-4-methyl-1-piperazinecarboxamide citrate (1:1)

Systematic Name

English

Classification Tree Code System Code

CFR

21 CFR 520.622B