RAFOXANIDE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H11Cl2I2NO3
Molecular Weight	626.01
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=C(I)C=C(I)C=C1C(=O)NC2=CC(Cl)=C(OC3=CC=C(Cl)C=C3)C=C2

InChI

InChIKey=NEMNPWINWMHUMR-UHFFFAOYSA-N

InChI=1S/C19H11Cl2I2NO3/c20-10-1-4-13(5-2-10)27-17-6-3-12(9-15(17)21)24-19(26)14-7-11(22)8-16(23)18(14)25/h1-9,25H,(H,24,26)

HIDE SMILES / InChI

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2009/11/WC500015821.pdf |

Rafoxanide is a halogenated salicylanilide used as a fasciolicide in cattle, sheep, goats, and horses. It is also active against nematodes, and the sheep nasal bot fly. Rafoxanide acts as by uncoupling oxidative phosphorylation of flukes, including reduced ATP levels, decreased glycogen content and accumulation of succinate.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
malate dehydrogenase activity 1 Target ID: GO:0016615 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7264272	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Fascioliasis 5 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2009/11/WC500015821.pdf https://www.drugs.com/international/rafoxanide.html	Primary		Approved 8583	Fenafluke Approved Use Rafoxanide is used as a fasciolicide in cattle, sheep, goats, and horses.

C_max

Value	Dose	Co-administered	Analyte	Population
35.4 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8691406/	7.5 mg/kg single, oral dose: 7.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		RAFOXANIDE plasma	Ovis aries population: HEALTHY age: ADULT sex: MALE food status: FASTED
19750 OTHER OTHER GOV'T https://www.ema.europa.eu/en/documents/mrl-report/rafoxanide-summary-report-1-committee-veterinary-medicinal-products_en.pdf	11.25 mg/kg bw single, oral dose: 11.25 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:		RAFOXANIDE plasma	Ovis aries population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
413.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8691406/	7.5 mg/kg single, oral dose: 7.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		RAFOXANIDE plasma	Ovis aries population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.5 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8691406/	7.5 mg/kg single, oral dose: 7.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		RAFOXANIDE plasma	Ovis aries population: HEALTHY age: ADULT sex: MALE food status: FASTED
8.9 day OTHER GOV'T https://www.ema.europa.eu/en/documents/mrl-report/rafoxanide-summary-report-1-committee-veterinary-medicinal-products_en.pdf	11.25 mg/kg bw single, oral dose: 11.25 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:		RAFOXANIDE plasma	Ovis aries population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% OTHER GOV'T https://www.ema.europa.eu/en/documents/mrl-report/rafoxanide-summary-report-1-committee-veterinary-medicinal-products_en.pdf	11.25 mg/kg bw single, oral dose: 11.25 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:		RAFOXANIDE plasma	Ovis aries population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP19A1 429 CYP2C19 2057	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/31475#section=BioAssay-Results Page: 184.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/31475#section=BioAssay-Results Page: 230.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/31475#section=BioAssay-Results Page: 230.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/31475#section=BioAssay-Results Page: 21.0	yes [EC50 22.3872 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/31475#section=BioAssay-Results Page: 18.0	yes [IC50 19.4971 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/31475#section=BioAssay-Results Page: 6.0	yes [IC50 2.754 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/31475#section=BioAssay-Results Page: 36.0	yes [IC50 38.9018 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/31475#section=BioAssay-Results Page: 16 \| 219	inconclusive

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/31475#section=BioAssay-Results Page: 229.0

PubMed

Title	Date	PubMed
An improved thyroid hormone reporter assay to determine the thyroid hormone-like activity of amiodarone, bithionol, closantel and rafoxanide.	2012-01-05	22015988
Quantitative analysis of closantel and rafoxanide in bovine and ovine muscles by high-performance liquid chromatography with fluorescence detection.	2010-12-15	21140680
Effect of three anthelmentics on disposition kinetics of florfenicol in goats.	2010-12	20863870
Interaction of anthelmintic drugs with P-glycoprotein in recombinant LLC-PK1-mdr1a cells.	2010-08-05	20513441
Biochemical analysis of a recombinant glutathione transferase from the cestode Echinococcus granulosus.	2010-04	20034460
Screening of closantel and rafoxanide in animal muscles by HPLC with fluorescence detection and confirmation using MS.	2010-02	19998374
Multi-residue determination of phenolic and salicylanilide anthelmintics and related compounds in bovine kidney by liquid chromatography-tandem mass spectrometry.	2009-11-13	19426989
Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening.	2009-07-14	19597541
The potential to control Haemonchus contortus in indigenous South African goats with copper oxide wire particles.	2009-06-10	19346076
Haemonchus contortus acetylcholine receptors of the DEG-3 subfamily and their role in sensitivity to monepantel.	2009-04	19360096
Comparative pharmacokinetics of ivermectin alone and a novel formulation of ivermectin and rafoxanide in calves and sheep.	2008-05	18297309
Comparative efficacy of different anthelmintics against fenbendazole-resistant nematodes of pashmina goats.	2007-08	17308986
A dual anthelmintic treatment strategic scheme for the control of fasciolosis in dairy sheep farms.	2006-11	16738889
Field trial on comparative efficacy of four fasciolicides against natural liver fluke infection in cattle.	2006-02-18	16289862
The Hymenolepis diminuta-golden hamster (Mesocricetus auratus) model for the evaluation of gastrointestinal anticestode activity.	2004-08	15357098
Anthelmintic resistance of nematodes in communally grazed goats in a semi-arid area of South Africa.	2003-09	15029952
Anthelmintic resistance on an organized sheep farm in India.	2001-07	11474864

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose range from 5 to 15 mg/kg bw is generally administered by oral gavage or by intra-ruminal route.

Route of Administration: Oral

In Vitro Use Guide

Flukes recovered from infected sheep were maintained in laboratory conditions in warm (37 deg-C) Hedon-Fleig saline and used within one hour of recovery. Rafoxanide tested in a concentration range of 0.01 to 1000 micro-g/mL as the commercial solutions, and in ethanol, dimethyl sulphoxide and Tween 80. Rafoxanide demonstrated faciolicide activity and a dose-response relationship. The motility of Fasciola hepatica was monitored by means of an isometric transducer connected to a high-speed pen recorder

Name

Type

Language

RAFOXANIDE

Official Name

English

NSC-355278

Preferred Name

English

N-(3-CHLORO-4-(4-CHLOROPHENOXY)PHENYL)-2-HYDROXY-3,5-DIIODOBENZAMIDE

Systematic Name

English

RAFOXANIDE [MART.]

Common Name

English

3'-CHLORO-4'-(4-CHLOROPHENOXY)-3,5-DIIODOSALICYLANILIDE

Systematic Name

English

rafoxanide [INN]

Common Name

English

BENZAMIDE, N-(3-CHLORO-4-(4-CHLOROPHENOXY)PHENYL)-2-HYDROXY-3,5-DIIODO-

Systematic Name

English

3'-CHLORO-4'-(P-CHLOROPHENOXY)-3,5-DIIODOSALICYLANILIDE

Common Name

English

RAFOXANIDE [MI]

Common Name

English

RAFOXANIDE [USAN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QP52AG05