| Identification |
|---|
| Name |
Metronidazole |
| Accession Number |
DB00916
(APRD00631)
|
| Type |
small molecule |
| Groups |
approved |
| Description |
A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). |
| Structure |
Download:
MOL |
SDF |
SMILES |
InChI
Display:
2D Structure |
3D Structure
|
| Synonyms |
- Methronidazole
- Metronidazol
- Metronidazole Benzoate
- Metronidazole Hcl
- Metronidazole in Plastic Container
- Metronidazolo
|
| Brand names |
- Acromona
- Anagiardil
- Apo-Metronidazole
- Arilin
- Atrivyl
- Bayer 5360
- Bexon
- Clont
- Cont
- Danizol
- Deflamon
- Deflamon-Wirkstoff
- Efloran
- Elyzol
- Entizol
- Eumin
- Flagemona
- Flagesol
- Flagil
- Flagyl
- Flagyl ER
- Flagyl I.V.
- Flegyl
- Fossyol
- Giatricol
- Gineflavir
- Klion
- Klont
- Meronidal
- Metric 21
- Metro Cream
- Metro I.V.
- Metro I.V. In Plastic Container
- Metrocream
- Metrogel
- Metrogel-Vaginal
- Metrolag
- Metrolotion
- Metrolyl
- Metromidol
- Metronidaz
- Metrotop
- Mexibol
- Monagyl
- Monasin
- Nalox
- Neo-Tric
- Nida
- Nidagel
- Noritate
- Novonidazol
- Orvagil
- Protostat
- Rathimed
- Sanatrichom
- Satric
- Takimetol
- Trichazol
- Trichex
- Tricho Cordes
- Tricho-Gynaedron
- Trichocide
- Trichomol
- Trichopal
- Trichopol
- Tricocet
- Tricom
- Tricowas B
- Trikacide
- Trikamon
- Trikojol
- Trikozol
- Trimeks
- Trivazol
- Vagilen
- Vagimid
- Vertisal
- Wagitran
- Zadstat
|
| Brand name mixtures |
- Helidac (Metronidazole + Bismuth subsalicylate + tetracycline hydrochloride)
|
| Categories |
- Anti-Infective Agents
- Anti-Infectives
- Radiation-Sensitizing Agents
- Antiprotozoals
- Antiprotozoal Agents
|
| CAS number |
443-48-1 |
| Weight |
Average: 171.154
Monoisotopic: 171.064391169
|
| Chemical Formula |
C6H9N3O3 |
| InChI Key |
InChIKey=VAOCPAMSLUNLGC-UHFFFAOYSA-N |
| InChI |
InChI=1S/C6H9N3O3/c1-5-7-4-6(9(11)12)8(5)2-3-10/h4,10H,2-3H2,1H3
Plain Text
|
| IUPAC Name |
2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethan-1-ol
|
| SMILES |
CC1=NC=C(N1CCO)[N+]([O-])=O
Plain Text
|
| Mass Spec |
show (9.7 KB)
|
| Taxonomy |
|---|
| Kingdom |
Organic |
| Classes |
|
| Substructures |
- Nitroimidazoles
- Hydroxy Compounds
- Oxoazaniums
- Nitro compounds
- Alcohols and Polyols
- Imidazoles
- Heterocyclic compounds
- Aromatic compounds
- Imines
- Cyanamides
|
| Pharmacology |
|---|
| Indication |
For the treatment of anaerobic infections and mixed infections, surgical prophylaxis requiring anaerobic coverage, Clostridium difficile-associated diarrhea and colitis, Helicobacter pylori infection and duodenal ulcer disease, bacterial vaginosis, Giardia lamblia gastro-enteritis, amebiasis caused by Entamoeba histolytica, acne rosacea (topical treatment), and Trichomonas infections. |
| Pharmacodynamics |
Metronidazole, a synthetic antibacterial and antiprotozoal agent of the nitroimidazole class, is used against protozoa such as Trichomonas vaginalis, amebiasis, and giardiasis. Metronidazole is extremely effective against anaerobic bacterial infections and is also used to treat Crohn's disease, antibiotic-associated diarrhea, and rosacea. |
| Mechanism of action |
Metronidazole is a prodrug. Unionized metronidazole is selective for anaerobic bacteria due to their ability to intracellularly reduce metronidazole to its active form. This reduced metronidazole then covalently binds to DNA, disrupt its helical structure, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death. |
| Absorption |
Well absorbed (at least 80%) with peak plasma concentrations achieved in 1-3 hours following oral administration of therapeutic doses of immediate release formulation. |
| Volume of distribution |
Not Available |
| Protein binding |
Less than 20% bound to plasma proteins. |
| Metabolism |
Hepatic metabolism by hydroxylation, oxidation, and glucuronidation.
|
| Route of elimination |
Not Available |
| Half life |
6-8 hours |
| Clearance |
Not Available |
| Toxicity |
LD50=500 mg/kg/day (orally in rat). Adverse effects include reversible peripheral neuropathy with prolonged therapy, CNS toxicity, disulfiram effect with alcohol, dark red-brown urine, metallic taste, nausea, epigastric distress, dizziness, vertigo and paresthesias associated with high doses, and neutropenia (reversible and mild). |
| Affected organisms |
|
| Pathways |
Not Available |
| Pharmacoeconomics |
|---|
| Manufacturers |
- Gd searle llc
- Able laboratories inc
- Alembic ltd
- Par pharmaceutical inc
- Galderma laboratories lp
- Altana inc
- G and w laboratories inc
- Sanofi aventis us llc
- Taro pharmaceutical industries ltd
- Tolmar inc
- Graceway pharmaceuticals llc
- Teva pharmaceuticals usa
- Baxter healthcare corp
- B braun medical inc
- Abbott laboratories pharmaceutical products div
- Abraxis pharmaceutical products
- Elkins sinn div ah robins co inc
- International medication systems ltd
- Watson laboratories inc
- Claris lifesciences ltd
- Hospira inc
- Laboratorios aplicaciones farmaceuticas sa de cv
- Halsey drug co inc
- Ivax pharmaceuticals inc sub teva pharmaceuticals usa
- Lnk international inc
- Mutual pharmaceutical co inc
- Pliva inc
- Sandoz inc
- Superpharm corp
- Teva pharmaceuticals usa inc
- World gen llc
- Ortho mcneil pharmaceutical inc
- Savage laboratories inc div altana inc
|
| Packagers |
|
| Dosage forms |
| Form |
Route |
Strength |
| Capsule |
Oral |
|
| Cream |
Intravaginal |
|
| Cream |
Topical |
|
| Gel |
Intravaginal |
|
| Gel |
Topical |
|
| Liquid |
Intravenous |
|
| Lotion |
Topical |
|
| Solution |
Intravenous |
|
| Tablet |
Oral |
|
| Tablet, extended release |
Oral |
|
|
| Prices |
| Unit description |
Cost |
Unit |
| MetroLotion 0.75% Lotion 59ml Bottle |
292.66 USD |
bottle |
| MetroCream 0.75% Cream 45 gm Tube |
281.09 USD |
tube |
| Metrogel 1% Gel 60 gm Tube |
200.93 USD |
tube |
| Metrogel 1% Kit Box |
200.93 USD |
box |
| Metrogel 1% kit |
193.2 USD |
kit |
| Noritate 1% Cream 60 gm Tube |
156.44 USD |
tube |
| MetroNIDAZOLE 0.75% Lotion 59ml Bottle |
89.86 USD |
bottle |
| MetroNIDAZOLE 0.75% Cream 45 gm Tube |
80.87 USD |
tube |
| MetroNIDAZOLE 0.75% Gel 45 gm Tube |
74.0 USD |
tube |
| MetroNIDAZOLE 0.75% Gel 70 gm Tube |
68.53 USD |
tube |
| Flagyl ER 750 mg 24 Hour tablet |
13.2 USD |
tablet |
| Flagyl er 750 mg tablet |
12.7 USD |
tablet |
| MetroNIDAZOLE 750 mg 24 Hour tablet |
8.07 USD |
tablet |
| Flagyl 500 mg tablet |
6.24 USD |
tablet |
| Metrocream 0.75% cream |
5.99 USD |
g |
| Danazol 200 mg capsule |
5.63 USD |
capsule |
| Flagyl 375 mg capsule |
5.45 USD |
capsule |
| Metrolotion topical 0.75% |
4.77 USD |
ml |
| Metronidazole benz powder |
4.74 USD |
g |
| Flagyl 250 mg tablet |
3.49 USD |
tablet |
| Danazol 100 mg capsule |
2.98 USD |
capsule |
| Noritate 1% cream |
2.51 USD |
g |
| Danazol 50 mg capsule |
1.99 USD |
capsule |
| Metronidazole powder |
1.65 USD |
g |
| Metronidazole 0.75% cream |
1.34 USD |
g |
| Metronidazole vaginal 0.75% gl |
0.94 USD |
g |
| Metronidazole 500 mg tablet |
0.72 USD |
tablet |
| Metrogel 0.75 % Gel |
0.69 USD |
g |
| Metrogel 1 % Gel |
0.63 USD |
g |
| Noritate 1 % Cream |
0.58 USD |
g |
| Rosasol 1 % Cream |
0.57 USD |
g |
| Metrocream 0.75 % Cream |
0.52 USD |
g |
| Metrolotion 0.75 % Lotion |
0.52 USD |
g |
| Metrogel-vaginal 0.75% gel |
0.51 USD |
g |
| Vandazole vaginal 0.75% gel |
0.48 USD |
g |
| Metronidazole 250 mg tablet |
0.44 USD |
tablet |
| Flagyl 10 % Cream |
0.25 USD |
g |
| Apo-Metronidazole 250 mg Tablet |
0.06 USD |
tablet |
| Flagyl 5 mg/ml |
0.03 USD |
ml |
| Metro iv 500 mg/100 ml |
0.03 USD |
ml |
| Metronidazole 5 mg/ml |
0.03 USD |
ml |
| Metronidazole 500 mg/100 ml |
0.03 USD |
ml |
|
| Patents |
| Country |
Patent Number |
Approved |
Expires |
| United States |
6881726 |
2002-02-21 |
2022-02-21 |
| United States |
5536743 |
1993-07-16 |
2013-07-16 |
| Canada |
2470492 |
2010-02-23 |
2022-11-07 |
| Canada |
2161737 |
1998-10-20 |
2015-10-30 |
|
| Properties |
|---|
| State |
solid |
| Melting point |
160 oC |
| Experimental Properties |
| Property |
Value |
Source |
| water solubility |
<0.1g/100mL |
PhysProp |
| logP |
-0.1 |
PhysProp |
| logS |
-1.26 [ADME Research, USCD] |
PhysProp |
|
| Predicted Properties |
|
| References |
|---|
| Synthesis Reference |
Not Available
|
| General Reference |
- Shennan A, Crawshaw S, Briley A, Hawken J, Seed P, Jones G, Poston L: A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study. BJOG. 2006 Jan;113(1):65-74. Pubmed
- Lamont RF: Can antibiotics prevent preterm birth—the pro and con debate. BJOG. 2005 Mar;112 Suppl 1:67-73. Pubmed
- Williams CS, Woodcock KR: Do ethanol and metronidazole interact to produce a disulfiram-like reaction? Ann Pharmacother. 2000 Feb;34(2):255-7. Pubmed
- Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP: Lack of disulfiram-like reaction with metronidazole and ethanol. Ann Pharmacother. 2002 Jun;36(6):971-4. Pubmed
|
| External Links |
|
| ATC Codes |
- A01AB17
- D06BX01
- G01AF01
- J01XD01
- P01AB01
|
| AHFS Codes |
- 84:04.92
- 84:04.04
- 08:30.92
|
| PDB Entries |
Not Available |
| FDA label |
show (115.5 KB)
|
| MSDS |
show (73.9 KB)
|
| Interactions |
|---|
| Drug Interactions |
Not Available |
| Food Interactions |
- Avoid alcohol.
- Take with food to reduce irritation.
|
| Targets |
|---|
1. DNA
Pharmacological action: yes
Actions: binder
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
Gene Sequence: FASTA
References:
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
- Salles JM, Salles MJ, Moraes LA, Silva MC: Invasive amebiasis: an update on diagnosis and management. Expert Rev Anti Infect Ther. 2007 Oct;5(5):893-901. Pubmed
- Li AQ, Dai N, Yan J, Zhu YL: [Screening for metronidazole-resistance associated gene fragments of Helicobacter pylori by suppression subtractive hybridization.] Zhejiang Da Xue Xue Bao Yi Xue Ban. 2007 Sep;36(5):465-9. Pubmed
- Edwards DI: Nitroimidazole drugs—action and resistance mechanisms. I. Mechanisms of action. J Antimicrob Chemother. 1993 Jan;31(1):9-20. Pubmed
2. Oxygen-insensitive NADPH nitroreductase
Pharmacological action: yes
Actions: potentiator
Organism class: bacterial
UniProt ID: O25608 
Gene: rdxA
SNPs: SNPJam Report
References:
- Sisson G, Jeong JY, Goodwin A, Bryden L, Rossler N, Lim-Morrison S, Raudonikiene A, Berg DE, Hoffman PS: Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H. pylori RdxA(+) (Nitroreductase) gene. J Bacteriol. 2000 Sep;182(18):5091-6. Pubmed
- Chisholm SA, Owen RJ: Mutations in Helicobacter pylori rdxA gene sequences may not contribute to metronidazole resistance. J Antimicrob Chemother. 2003 Apr;51(4):995-9. Epub 2003 Mar 13. Pubmed
- Debets-Ossenkopp YJ, Pot RG, van Westerloo DJ, Goodwin A, Vandenbroucke-Grauls CM, Berg DE, Hoffman PS, Kusters JG: Insertion of mini-IS605 and deletion of adjacent sequences in the nitroreductase (rdxA) gene cause metronidazole resistance in Helicobacter pylori NCTC11637. Antimicrob Agents Chemother. 1999 Nov;43(11):2657-62. Pubmed
- Pisharath H, Parsons MJ: Nitroreductase-mediated cell ablation in transgenic zebrafish embryos. Methods Mol Biol. 2009;546:133-43. Pubmed
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
3. Periplasmic [Fe] hydrogenase 1
Pharmacological action: unknown
Actions: inhibitor
Organism class: bacterial
UniProt ID: P29166
Protein Sequence: FASTA
Gene Sequence: FASTA
References:
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
- Kutty R, Bennett GN: Studies on inhibition of transformation of 2,4,6-trinitrotoluene catalyzed by Fe-only hydrogenase from Clostridium acetobutylicum. J Ind Microbiol Biotechnol. 2006 May;33(5):368-76. Epub 2006 Jan 28. Pubmed
|
| Enzymes |
|---|
1. Cytochrome P450 2C9
Actions: substrate, inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan
UniProt ID: P11712
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
2. Cytochrome P450 3A4
Actions: substrate, inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide
UniProt ID: P08684
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
3. Cytochrome P450 2C8
Actions: inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)
UniProt ID: P10632
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
|
