Secnidazole

Identification

Name
Secnidazole
Accession Number
DB12834
Type
Small Molecule
Groups
Approved
Description

Secnidazole is a second-generation 5-nitroimidazole antimicrobial that is structurally related to other 5-nitroimidazoles including Metronidazole and Tinidazole, but displays improved oral absorption and longer terminal elimination half-life than antimicrobial agents in this class [1]. Secnidazole is selective against many anaerobic Gram-positive and Gram-negative bacteria and protozoa. In September 2017, FDA granted approval to secnidazole under the market name Solosec as a single-dose oral treatment for bacterial vaginosis, which is a common vaginal infection in women aged 15 to 44 years. The antimicrobial therapy is only intended to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria [FDA Label].

Structure
Thumb
Synonyms
  • 1-(2­ hydroxypropyl)-2-methyl-5-nitroimidazole
  • 1-(2-methyl-5-nitro-1H-imidazol-1-yl) propan-2­ ol
External IDs
SYM-1219
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SolosecGranule2 g/4.8gOralSymbiomix Therapeutics2017-09-292017-11-01Us
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SolosecGranule2 g/4.8gOralLupin Pharma2017-10-30Not applicableUs
Categories
UNII
R3459K699K
CAS number
3366-95-8
Weight
Average: 185.183
Monoisotopic: 185.080041226
Chemical Formula
C7H11N3O3
InChI Key
KPQZUUQMTUIKBP-UHFFFAOYSA-N
InChI
InChI=1S/C7H11N3O3/c1-5(11)4-9-6(2)8-3-7(9)10(12)13/h3,5,11H,4H2,1-2H3
IUPAC Name
1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ol
SMILES
CC(O)CN1C(C)=NC=C1N(=O)=O

Pharmacology

Indication

Indicated for the treatment of bacterial vaginosis in adult women .

Structured Indications
Not Available
Pharmacodynamics

Secnidazole is a nitroimidazole antimicrobial drug that displays selectivity against many anaerobic Gram-positive and Gram-negative bacteria and protozoa [1]. In vitro studies demonstrates the effectiveness of the drug against Bacteroides fragilis, Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia [1]. There is no significant bacterial or protozoal resistance reported from secnidazole treatment [1].

Mechanism of action

Secnidazole enters the bacterial cell as a prodrug without an antimicrobial activity. The drug is converted to an active form via reduction of nitro groups to radical anions by bacterial enzymes. The radical anions are thought to interfere with bacterial DNA synthesis of susceptible isolates [FDA Label].

Absorption

Secnidazole is rapidly and completely absorbed after oral administration [1]. Following a single oral dose of 2 g in healthy adult female subjects, the mean (SD) secnidazole peak plasma concentration (Cmax) of 45.4 (7.64) mcg/mL and mean (SD) systemic exposure (AUC0-inf) of 1331.6 (230.16) mcg x hr/mL was reached. Median (range) time to peak concentration (Tmax) was 4.0 (3.0-4.0) hours [FDA Label].

Volume of distribution

The apparent volume of distribution of secnidazole is approximately 42-49 L [FDA Label].

Protein binding

The plasma protein binding of secnidazole is < 5-15% [FDA Label].

Metabolism

According to in vitro studies, secnidazole is metabolized via oxidation by human hepatic CYP450 enzyme system with ≤ 1% conversion to metabolites [FDA Label].

Route of elimination

The predominant route of elimination is renal elimination. Following a single oral dose of 2g secnidazole, approximately 15% of the drug is excreted as unchanged compoung in the urine [FDA Label].

Half life

The plasma elimination half-life for secnidazole is approximately 17 hours [FDA Label].

Clearance

The total body clearance of secnidazole is approximately 25 mL/min. The renal clearance of secnidazole is approximately 3.9 mL/min [FDA Label].

Toxicity

Oral LD50 in mouse, rabbit and rat is 300 mg/kg, 3200 mg/kg and 980 mg/kg, in a respective order [MSDS]. Secnidazole was positive in the Bacterial Reverse Mutation Assay, but was negative for the rat micronucleus test and mouse lymphoma test. No parental toxicity or signs of reproductive toxicity were observed in female rat fertility studies at doses of up to the maximum tolerated dose of 300 mg/kg/day [FDA Label].

Affected organisms
  • Trichomonas vaginalis, Giardia duodenalis, and Entamoeba histolytica
  • Bacteria and protozoa
  • Bacteroides fragilis
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Gillis JC, Wiseman LR: Secnidazole. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic use in the management of protozoal infections and bacterial vaginosis. Drugs. 1996 Apr;51(4):621-38. [PubMed:8706597]
External Links
PubChem Compound
71815
PubChem Substance
347829000
ChemSpider
64839
BindingDB
50349330
ChEBI
94433
ChEMBL
CHEMBL498847
ATC Codes
P01AB07 — SecnidazoleJ01RA07 — Azithromycin, fluconazole and secnidazole
FDA label
Download (344 KB)
MSDS
Download (78.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedBasic ScienceCholera / Salmonella Typhi Infection1
2CompletedTreatmentBacterial Vaginosis (BV)1
3CompletedTreatmentBacterial Vaginosis (BV)2
3CompletedTreatmentVaginal Discharge1
3TerminatedTreatmentDiverticular Sigmoïditis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
GranuleOral2 g/4.8g
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.88 mg/mLALOGPS
logP0.25ALOGPS
logP-0.043ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)15.16ChemAxon
pKa (Strongest Basic)3.08ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area83.87 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity45.64 m3·mol-1ChemAxon
Polarizability17.57 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004r-0900000000-4607b9260ff959d777e0
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-3900000000-b3c36444a446482a04bc

Taxonomy

Description
This compound belongs to the class of organic compounds known as nitroimidazoles. These are compounds containing an imidazole ring which bears a nitro group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Imidazoles
Direct Parent
Nitroimidazoles
Alternative Parents
Nitroaromatic compounds / 1,2,5-trisubstituted imidazoles / N-substituted imidazoles / Heteroaromatic compounds / Secondary alcohols / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
show 3 more
Substituents
1,2,5-trisubstituted-imidazole / Nitroaromatic compound / Nitroimidazole / Trisubstituted imidazole / N-substituted imidazole / Heteroaromatic compound / C-nitro compound / Secondary alcohol / Organic nitro compound / Organic oxoazanium
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Drug created on October 20, 2016 18:36 / Updated on November 16, 2017 13:42