SECNIDAZOLE

Details

Stereochemistry	RACEMIC
Molecular Formula	C7H11N3O3
Molecular Weight	185.1805
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(O)CN1C(C)=NC=C1[N+]([O-])=O

InChI

InChIKey=KPQZUUQMTUIKBP-UHFFFAOYSA-N

InChI=1S/C7H11N3O3/c1-5(11)4-9-6(2)8-3-7(9)10(12)13/h3,5,11H,4H2,1-2H3

HIDE SMILES / InChI

Description
Sources: http://reference.medscape.com/drug/formulary/solosec-secnidazole-1000168#0

Secnidazole (trade names Flagentyl, Sindose, Solosec) is a nitroimidazole derivative used to in the treatment of amoebiasis and bacterial vaginosis. Secnidazole and other 5-nitroimidazole drugs enter micro-organisms by passive diffusion and undergo activation by reduction of the 5-nitro group. In anaerobic micro-organisms, such as Trichomonas, Giardia and Entamoeba spp., this intracellular reduction occurs via the pyruvate ferredoxin oxidoreductase complex and results in a concentration gradient across the cell membrane which, in tum, enhances transport of the parent drug into the cell. Because the electron affinity of the 5-nitroimidazoles is greater than that of reduced ferredoxin, the drug interrupts the normal electron flow. Aerobic micro-organisms have a more positive redox potential (i.e. are more efficient electron acceptors) than secnidazole and other 5-nitroimidazoles, which explains the selective toxicity of these drugs against anaerobic microorganisms. DNA is the intracellular target of the Secnidazole and other 5-nitroimidazoles. Secnidazole and other 5-nitroimidazoles possess selective activity against many anaerobic Gram-positive and Gram-negative bacteria and protozoa. In general, secnidazole and metronidazole were approximately equipotent in activity against Bacteroides fragilis, Trichomonas vaginalis, and Entamoeba histolytica, in in vitro studies. Secnidazole is rapidly and completely absorbed after oral administration. Plasma drug concentrations are linear over the therapeutic dose range of 0.5 to 2g. The tolerability profile of secnidazole does not differ markedly from other 5-nitroimidazoles. The most commonly reported adverse events in clinical trials involved the gastrointestinal tract (nausea, vomiting, glossitis, anorexia, epigastric pain and a metallic taste) and occurred in 2 to 10% of patients. A headache and dizziness were experienced by about 2% of patients. The drug was equally well tolerated in adults and children, and no adverse event required therapeutic intervention or treatment withdrawal.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Trichomonas vaginalis 11 Target ID: CHEMBL612884 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18590939	Inhibitor 8297		810.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Bacterial vaginosis 10 Sources: http://reference.medscape.com/drug/solosec-secnidazole-1000168	Curative		Approved 8429	Solosec Approved Use Unknown
Giardiasis 12 Sources: https://clinicaltrials.gov/ct2/show/NCT00607074	Curative		Approved 8429	Solosec Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
45.4 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SECNIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
1410 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SECNIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
17.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SECNIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
95% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SECNIDAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

Doses

Dose	Population	Adverse events
2 g single, oral Recommended Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1	unhealthy, 15 - 54 years n = 197 Health Status: unhealthy Condition: bacterial vaginosis Age Group: 15 - 54 years Sex: F Population Size: 197 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1	Other AEs: Vulvovaginal candidiasis, Headache... Other AEs: Vulvovaginal candidiasis (9.6%) Headache (3.6%) Nausea (3.6%) Diarrhea (2.5%) Abdominal pain (2%) Vulvovaginal pruritus (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1
1 g single, oral Studied dose Dose: 1 g Route: oral Route: single Dose: 1 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: 6.1	unhealthy, 15 - 54 years n = 71 Health Status: unhealthy Condition: bacterial vaginosis Age Group: 15 - 54 years Sex: F Population Size: 71 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: 6.1	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: 6.1

AEs

AE	Significance	Dose	Population
Abdominal pain	2%	2 g single, oral Recommended Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1	unhealthy, 15 - 54 years n = 197 Health Status: unhealthy Condition: bacterial vaginosis Age Group: 15 - 54 years Sex: F Population Size: 197 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1
Vulvovaginal pruritus	2%	2 g single, oral Recommended Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1	unhealthy, 15 - 54 years n = 197 Health Status: unhealthy Condition: bacterial vaginosis Age Group: 15 - 54 years Sex: F Population Size: 197 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1
Diarrhea	2.5%	2 g single, oral Recommended Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1	unhealthy, 15 - 54 years n = 197 Health Status: unhealthy Condition: bacterial vaginosis Age Group: 15 - 54 years Sex: F Population Size: 197 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1
Headache	3.6%	2 g single, oral Recommended Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1	unhealthy, 15 - 54 years n = 197 Health Status: unhealthy Condition: bacterial vaginosis Age Group: 15 - 54 years Sex: F Population Size: 197 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1
Nausea	3.6%	2 g single, oral Recommended Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1	unhealthy, 15 - 54 years n = 197 Health Status: unhealthy Condition: bacterial vaginosis Age Group: 15 - 54 years Sex: F Population Size: 197 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1
Vulvovaginal candidiasis	9.6%	2 g single, oral Recommended Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1	unhealthy, 15 - 54 years n = 197 Health Status: unhealthy Condition: bacterial vaginosis Age Group: 15 - 54 years Sex: F Population Size: 197 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209363s000lbl.pdf Page: Table 1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 inhibitor 1587 substrate 1737	inducer 389 inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 599 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 P-gp 1461 BCRP 699 OATP1B1 788 OATP1B3 706 OAT3 642 OCT2 647 ALDH2 19	CYP1A2 1054 CYP2B6 664 CYP2C8 693 CYP3A5 395 P-gp 1537 BCRP 561 OATP1B1 406 OATP1B3 350 OAT1 326 OAT3 339 OCT2 355	CYP1A2 701 CYP2B6 547 CYP2C8 168 CYP2C19 293

Drug as perpetrator

Target	Modality	Activity
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=56 Page: 9, 18, 54-56	no [IC50 3873 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=56 Page: 9, 18, 54-56	no [IC50 4306 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=56 Page: 10, 18, 54-56	no [IC50 >5000 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=56 Page: 10, 18, 54-56	no [IC50 >5000 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=56 Page: 10, 18, 54-56	no [IC50 >5000 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=56 Page: 10, 18, 54-56	no [IC50 >5000 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=56 Page: 10, 18, 54-56	no [IC50 >5000 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=56 Page: 10, 18, 54-56	no [IC50 >5000 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=56 Page: 10, 18, 54-56	no [IC50 >5000 uM]
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 10, 62, 64-65	unlikely [Inhibition 2300 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 10, 62, 64-65	unlikely [Inhibition 2300 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 10, 62, 64-65	unlikely [Inhibition 2300 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 10, 62, 64-65	unlikely [Inhibition 2400 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 10, 62, 64-65	unlikely [Inhibition 2400 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=64 Page: 10, 61, 63-64	unlikely [Inhibition 4300 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=64 Page: 10, 61, 63-64	unlikely [Inhibition 4300 uM]
ALDH2 19	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 17, 65-68	weak [IC50 503 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=10 Page: 9, 18, 50-52	yes
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=10 Page: 9, 18, 50-52	yes
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=10 Page: 9, 18, 50-52	yes
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=10 Page: 9, 18, 50-52	yes
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=10 Page: 9, 18, 50-52	yes
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=10 Page: 9, 18, 50-52	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=58 Page: 57-59	inconclusive
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=58 Page: 57-59	inconclusive
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=58 Page: 57-59	minor
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=63 Page: 18, 61-63	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 18, 62, 64-65	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 18, 62, 64-65	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 18, 62, 64-65	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 18, 62, 64-65	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=65 Page: 18, 62, 64-65	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=63 Page: 18, 61-63	no
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=58 Page: 57-59	yes
CYP3A5 395	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000ClinPharmR.pdf#page=58 Page: 57-59	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209363Orig1s000PharmR.pdf#page=13 Page: 24.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:140628	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:140628
ChemicalBook	CB7372041	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7372041
MolPort	MolPort-000-811-111	https://www.molport.com/shop/molecule-link/MolPort-000-811-111
Selleck Chemicals	Secnidazole-Flagentyl	http://www.selleckchem.com/products/Secnidazole-Flagentyl.html
eMolecules	902453	https://www.emolecules.com/cgi-bin/more?vid=902453

PubMed

Title	Date	PubMed
Randomized trial of a quadruple-drug regimen and a triple-drug regimen for eradication of Helicobacter pylori: long-term follow-up study.	2001 Sep-Oct	11676331
Low efficacy of an ultra-short term, once-daily dose triple therapy with omeprazole, azithromycin, and secnidazole for Helicobacter pylori eradication in peptic ulcer.	2002 Jan-Feb	12170343
Pre and post eradication gastric inflammation in Helicobacter pylori-associated duodenal ulcer.	2002 Jan-Feb	11871846
[New drugs for the treatment of human parasitic protozoa].	2004 Jun	15305692
Prescription of fixed dose combination drugs for diarrhoea.	2007 Oct-Dec	18630234
Formulation and evaluation of PLA and PLGA in situ implants containing secnidazole and/or doxycycline for treatment of periodontitis.	2008	18654864
Short-term triple therapy with azithromycin for Helicobacter pylori eradication: low cost, high compliance, but low efficacy.	2008 May 29	18510773
The concept of personal drugs in the undergraduate pharmacology practical curriculum.	2008 Nov	21279187
The old and new therapeutic approaches to the treatment of giardiasis: where are we?	2009	19707415
Impact of anti-Giardia and anthelminthic treatment on infant growth and intestinal permeability in rural Bangladesh: a randomised double-blind controlled study.	2009 May	18789466
A Stability-Indicating RP-HPLC Assay Method for 5-Fluorouracil.	2009 Nov	20376215
Infectious diseases and prematurity.	2010	21512590
Treatment of bacterial vaginosis: a multicenter, double-blind, double-dummy, randomised phase III study comparing secnidazole and metronidazole.	2010	20885970
[Using safocid for antibiotic prophylaxis in minimally-invasive endoscopic operations and manipulations].	2010 Nov-Dec	21427992

Patents

Sample Use Guides

In Vivo Use Guide

2g as single-dose oral dose

Route of Administration: Oral

In Vitro Use Guide

In vitro toxicity of nitroimidazoles was assessed on human monocytes (THP1 cells) maintained at 37 C in 6% CO2, in a medium of RPMI (Eurobio, Paris, France) supplemented with 10% foetal calf serum (Eurobio, Paris, France), 25 mM of HEPES, 25 mM of NaHCO3 (Gibco-BRL, Paisley, Scotland), and 1% of L-glutamine/penicillinestreptomycin mix. THP1 cell (105 cells/mL) were incubated with different concentrations of Secnidazole dissolved in DMSO. A viability control free of drug and a control containing DMSO (final concentration of 0.5%) were performed in parallel. After a 72 h-incubation at 37 C and 6% CO2 in complete RPMI medium, cell growth and viability were measured by flow cytometry after staining the monocytes by 5 mL of propidium iodide (1 mg/mL)

Name

Type

Language

SECNIDAZOLE

Official Name

English

SECNIDAZOLE [MART.]

Common Name

English

ORNIDAZOLE METABOLITE M4

Common Name

English

PM-185184

Code

English

Secnidazole [WHO-DD]

Common Name

English

SECNIDAZOLE [MI]

Common Name

English

secnidazole [INN]

Common Name

English

SECNIDAZOLE [ORANGE BOOK]

Common Name

English

RP 14539

Code

English

SOLOSEC

Brand Name

English

RP-14539

Code

English

1H-IMIDAZOLE-1-ETHANOL, .ALPHA.,2-DIMETHYL-5-NITRO-

Systematic Name

English

.ALPHA.,2-DIMETHYL-5-NITROIMIDAZOLE-1-ETHANOL

Systematic Name

English

NSC-759812

Code

English

SECNIDAL

Brand Name

English

SECNIDAZOLE ANHYDROUS

Common Name

English

SECNIDAZOLE [USAN]

Common Name

English

SYM-1219

Code

English

Classification Tree Code System Code

NDF-RT

N0000175435