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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 Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Methronidazole
Metronidazol
Metronidazole Benzoate
Metronidazole Hcl
Metronidazole in Plastic Container
Metronidazolo
Salts Not Available
Brand names
Name Company
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
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Brand mixtures
Brand Name Ingredients
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 (9.68 KB)
Taxonomy
Kingdom Organic
Classes
  • Nitroimidazoles
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
  • Bacteria and protozoa
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
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
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
Experimental Properties
Property Value Source
melting point 160.5 °C PhysProp
water solubility 9500 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP -0.02 HANSCH,C ET AL. (1995)
logS -1.26 ADME Research, USCD
Predicted Properties
Property Value Source
water solubility 5.92e+00 g/l ALOGPS
logP -0.15 ALOGPS
logP -0.46 ChemAxon
logS -1.5 ALOGPS
pKa (strongest acidic) 15.44 ChemAxon
pKa (strongest basic) 3.09 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 83.87 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 41.22 ChemAxon
polarizability 15.82 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. 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
  2. Lamont RF: Can antibiotics prevent preterm birth—the pro and con debate. BJOG. 2005 Mar;112 Suppl 1:67-73. Pubmed
  3. Williams CS, Woodcock KR: Do ethanol and metronidazole interact to produce a disulfiram-like reaction? Ann Pharmacother. 2000 Feb;34(2):255-7. Pubmed
  4. 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
Resource Link
KEGG Drug D00409 Link_out
PubChem Compound 4173 Link_out
PubChem Substance 46508911 Link_out
ChemSpider 4029 Link_out
ChEBI 6909 Link_out
ChEMBL 6909 Link_out
Therapeutic Targets Database DAP000534 Link_out
PharmGKB PA450484 Link_out
Drug Product Database 649074 Link_out
RxList http://www.rxlist.com/cgi/generic/metron.htm Link_out
Drugs.com http://www.drugs.com/metronidazole.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Metronidazole Link_out
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 KB)
MSDS show (73.9 KB)
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol Metronidazole may increase the anticoagulant effect of acenocoumarol.
Amobarbital The barbiturate, amobarbital, decreases the effect of metronidazole.
Amprenavir Increased risk of side effects (oral solution)
Anisindione Metronidazole may increase the anticoagulant effect of anisindione.
Aprobarbital The barbiturate, aprobarbital, decreases the effect of metronidazole.
Busulfan Metronidazole increases the effect/toxicity of busulfan
Butabarbital The barbiturate, butabarbital, decreases the effect of metronidazole.
Butalbital The barbiturate, butalbital, decreases the effect of metronidazole.
Butethal The barbiturate, butethal, decreases the effect of metronidazole.
Carbamazepine Metronidazole increases the effect of carbamazepine
Dicumarol Metronidazole may increase the anticoagulant effect of dicumarol.
Dihydroquinidine barbiturate The barbiturate, dihydroquinidine barbiturate, decreases the effect of metronidazole.
Disulfiram Possible acute psychosis and confusion
Fluorouracil Risk of 5-FU toxicity when associated with metronidazole
Heptabarbital The barbiturate, heptabarbital, decreases the effect of metronidazole.
Hexobarbital The barbiturate, hexobarbital, decreases the effect of metronidazole.
Lithium Metronidazole increases the effect and toxicity of lithium
Methohexital The barbiturate, methohexital, decreases the effect of metronidazole.
Methylphenobarbital The barbiturate, methylphenobarbital, decreases the effect of metronidazole.
Pentobarbital The barbiturate, pentobarbital, decreases the effect of metronidazole.
Phenobarbital The barbiturate, phenobarbital, decreases the effect of metronidazole.
Primidone The barbiturate, primidone, decreases the effect of metronidazole.
Quinidine barbiturate The barbiturate, quinidine barbiturate, decreases the effect of metronidazole.
Secobarbital The barbiturate, secobarbital, decreases the effect of metronidazole.
Tacrolimus Metronidazole increases the levels/toxicity of tacrolimus
Talbutal The barbiturate, talbutal, decreases the effect of metronidazole.
Tamsulosin Metronidazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Metronidazole is initiated, discontinued, or dose changed.
Tolterodine Metronidazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tramadol Metronidazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inhibitor, Metronidazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Metronidazole is initiated, discontinued or dose changed.
Warfarin Metronidazole may increase the serum concentration of warfarin by decreasing its metabolism. Consider alternate therapy or a dose reduction in warfarin. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if metronidazole is initiated, discontinued or dose changed.
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:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
  3. 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
  4. 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
  5. 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 Link_out
Gene: rdxA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. Pisharath H, Parsons MJ: Nitroreductase-mediated cell ablation in transgenic zebrafish embryos. Methods Mol Biol. 2009;546:133-43. Pubmed
  5. 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 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
  3. 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 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19