You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameMetronidazole
Accession NumberDB00916  (APRD00631)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
1-(2-hydroxy-1-ethyl)-2-methyl-5-nitroimidazoleNot AvailableNot Available
1-(2-hydroxyethyl)-2-methyl-5-nitroimidazoleNot AvailableNot Available
1-(β-ethylol)-2-methyl-5-nitro-3-azapyrroleNot AvailableNot Available
1-(β-hydroxyethyl)-2-methyl-5-nitroimidazoleNot AvailableNot Available
1-(β-oxyethyl)-2-methyl-5-nitroimidazoleNot AvailableNot Available
2-methyl-1-(2-hydroxyethyl)-5-nitroimidazoleNot AvailableNot Available
2-methyl-3-(2-hydroxyethyl)-4-nitroimidazoleNot AvailableNot Available
2-methyl-5-nitroimidazole-1-ethanolNot AvailableNot Available
Salts
Name/CAS Structure Properties
Metronidazole hydrochloride
69198-10-3
Thumb
  • InChI Key: FPTPAIQTXYFGJC-UHFFFAOYSA-N
  • Monoisotopic Mass: 207.041068908
  • Average Mass: 207.615
DBSALT000362
Brand names
NameCompany
AcromonaNot Available
AnabactCambridge Healthcare Supplies
ArilinNot Available
ClontNot Available
DeflamonNot Available
EfloranNot Available
ElyzolNot Available
EntizolNot Available
FlagylNot Available
FossyolNot Available
KlionNot Available
KlontNot Available
MetroCreamNot Available
MetrogelNot Available
Metrogel-VaginalNot Available
MetroLotionNot Available
MetrolylNot Available
MetrotopNot Available
NaloxNot Available
NidagelNot Available
NoritateNot Available
NovonidazolNot Available
OrvagilNot Available
ProtostatNot Available
RosadanNot Available
TakimetolNot Available
TrichazoleNot Available
TrichexNot Available
TrichopolNot Available
Tricowas BNot Available
TrikacideNot Available
TrikozolNot Available
VagilenNot Available
VagimidNot Available
VandazoleNot Available
VertisalNot Available
ZadstatNot Available
Brand mixtures
Brand NameIngredients
HelidacMetronidazole + Bismuth subsalicylate + tetracycline hydrochloride
Categories
CAS number443-48-1
WeightAverage: 171.154
Monoisotopic: 171.064391169
Chemical FormulaC6H9N3O3
InChI KeyVAOCPAMSLUNLGC-UHFFFAOYSA-N
InChI
InChI=1S/C6H9N3O3/c1-5-7-4-6(9(11)12)8(5)2-3-10/h4,10H,2-3H2,1H3
IUPAC Name
2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethan-1-ol
SMILES
CC1=NC=C(N1CCO)[N+]([O-])=O
Mass Specshow(9.68 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassAzoles
SubclassImidazoles
Direct parentNitroimidazoles
Alternative parentsTrisubstituted Imidazoles; N-substituted Imidazoles; Nitronic Acids; Nitro Compounds; Polyamines; Primary Alcohols; Organic Oxoazanium Compounds
Substituentsn-substituted imidazole; nitronic acid; nitro compound; polyamine; primary alcohol; organic oxoazanium; alcohol; organonitrogen compound; amine
Classification descriptionThis compound belongs to the nitroimidazoles. These are compounds containing an imidazole ring which bears a nitro group.
Pharmacology
IndicationFor 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.
PharmacodynamicsMetronidazole, 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 actionMetronidazole 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.
AbsorptionWell 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 distributionNot Available
Protein bindingLess than 20% bound to plasma proteins.
Metabolism

Hepatic metabolism by hydroxylation, oxidation, and glucuronidation.

Route of eliminationNot Available
Half life6-8 hours
ClearanceNot Available
ToxicityLD50=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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9805
Blood Brain Barrier + 0.9297
Caco-2 permeable - 0.5365
P-glycoprotein substrate Non-substrate 0.5141
P-glycoprotein inhibitor I Non-inhibitor 0.8954
P-glycoprotein inhibitor II Non-inhibitor 0.8755
Renal organic cation transporter Non-inhibitor 0.7762
CYP450 2C9 substrate Non-substrate 0.7318
CYP450 2D6 substrate Non-substrate 0.8815
CYP450 3A4 substrate Non-substrate 0.6767
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9242
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9401
CYP450 3A4 substrate Non-inhibitor 0.9242
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8483
Ames test AMES toxic 0.9107
Carcinogenicity Non-carcinogens 0.7471
Biodegradation Not ready biodegradable 0.5941
Rat acute toxicity 2.0422 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.5
hERG inhibition (predictor II) Non-inhibitor 0.8272
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
FormRouteStrength
CapsuleOral
CreamIntravaginal
CreamTopical
GelIntravaginal
GelTopical
LiquidIntravenous
LotionTopical
SolutionIntravenous
TabletOral
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
MetroLotion 0.75% Lotion 59ml Bottle292.66USDbottle
MetroCream 0.75% Cream 45 gm Tube281.09USDtube
Metrogel 1% Gel 60 gm Tube200.93USDtube
Metrogel 1% Kit Box200.93USDbox
Metrogel 1% kit193.2USDkit
Noritate 1% Cream 60 gm Tube156.44USDtube
MetroNIDAZOLE 0.75% Lotion 59ml Bottle89.86USDbottle
MetroNIDAZOLE 0.75% Cream 45 gm Tube80.87USDtube
MetroNIDAZOLE 0.75% Gel 45 gm Tube74.0USDtube
MetroNIDAZOLE 0.75% Gel 70 gm Tube68.53USDtube
Flagyl ER 750 mg 24 Hour tablet13.2USDtablet
Flagyl er 750 mg tablet12.7USDtablet
MetroNIDAZOLE 750 mg 24 Hour tablet8.07USDtablet
Flagyl 500 mg tablet6.24USDtablet
Metrocream 0.75% cream5.99USDg
Danazol 200 mg capsule5.63USDcapsule
Flagyl 375 mg capsule5.45USDcapsule
Metrolotion topical 0.75%4.77USDml
Metronidazole benz powder4.74USDg
Flagyl 250 mg tablet3.49USDtablet
Danazol 100 mg capsule2.98USDcapsule
Noritate 1% cream2.51USDg
Danazol 50 mg capsule1.99USDcapsule
Metronidazole powder1.65USDg
Metronidazole 0.75% cream1.34USDg
Metronidazole vaginal 0.75% gl0.94USDg
Metronidazole 500 mg tablet0.72USDtablet
Metrogel 0.75 % Gel0.69USDg
Metrogel 1 % Gel0.63USDg
Noritate 1 % Cream0.58USDg
Rosasol 1 % Cream0.57USDg
Metrocream 0.75 % Cream0.52USDg
Metrolotion 0.75 % Lotion0.52USDg
Metrogel-vaginal 0.75% gel0.51USDg
Vandazole vaginal 0.75% gel0.48USDg
Metronidazole 250 mg tablet0.44USDtablet
Flagyl 10 % Cream0.25USDg
Apo-Metronidazole 250 mg Tablet0.06USDtablet
Flagyl 5 mg/ml0.03USDml
Metro iv 500 mg/100 ml0.03USDml
Metronidazole 5 mg/ml0.03USDml
Metronidazole 500 mg/100 ml0.03USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States68817262002-02-212022-02-21
United States55367431993-07-162013-07-16
Canada24704922010-02-232022-11-07
Canada21617371998-10-202015-10-30
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point160.5 °CPhysProp
water solubility9500 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-0.02HANSCH,C ET AL. (1995)
logS-1.26ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility5.92e+00 g/lALOGPS
logP-0.15ALOGPS
logP-0.46ChemAxon
logS-1.5ALOGPS
pKa (strongest acidic)15.44ChemAxon
pKa (strongest basic)3.09ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count1ChemAxon
polar surface area83.87ChemAxon
rotatable bond count3ChemAxon
refractivity41.22ChemAxon
polarizability15.82ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US2944061
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
ResourceLink
KEGG DrugD00409
PubChem Compound4173
PubChem Substance46508911
ChemSpider4029
ChEBI6909
ChEMBLCHEMBL137
Therapeutic Targets DatabaseDAP000534
PharmGKBPA450484
Drug Product Database649074
RxListhttp://www.rxlist.com/cgi/generic/metron.htm
Drugs.comhttp://www.drugs.com/metronidazole.html
WikipediaMetronidazole
ATC CodesA01AB17D06BX01G01AF01J01XD01P01AB01
AHFS Codes
  • 84:04.92
  • 84:04.04
  • 08:30.92
PDB EntriesNot Available
FDA labelshow(115 KB)
MSDSshow(73.9 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolMetronidazole may increase the anticoagulant effect of acenocoumarol.
AmobarbitalThe barbiturate, amobarbital, decreases the effect of metronidazole.
AmprenavirIncreased risk of side effects (oral solution)
AnisindioneMetronidazole may increase the anticoagulant effect of anisindione.
AprobarbitalThe barbiturate, aprobarbital, decreases the effect of metronidazole.
BusulfanMetronidazole increases the effect/toxicity of busulfan
ButabarbitalThe barbiturate, butabarbital, decreases the effect of metronidazole.
ButalbitalThe barbiturate, butalbital, decreases the effect of metronidazole.
ButethalThe barbiturate, butethal, decreases the effect of metronidazole.
CarbamazepineMetronidazole increases the effect of carbamazepine
DicoumarolMetronidazole may increase the anticoagulant effect of dicumarol.
Dihydroquinidine barbiturateThe barbiturate, dihydroquinidine barbiturate, decreases the effect of metronidazole.
DisulfiramPossible acute psychosis and confusion
FluorouracilRisk of 5-FU toxicity when associated with metronidazole
HeptabarbitalThe barbiturate, heptabarbital, decreases the effect of metronidazole.
HexobarbitalThe barbiturate, hexobarbital, decreases the effect of metronidazole.
LithiumMetronidazole increases the effect and toxicity of lithium
MethohexitalThe barbiturate, methohexital, decreases the effect of metronidazole.
MethylphenobarbitalThe barbiturate, methylphenobarbital, decreases the effect of metronidazole.
PentobarbitalThe barbiturate, pentobarbital, decreases the effect of metronidazole.
PhenobarbitalThe barbiturate, phenobarbital, decreases the effect of metronidazole.
PrimidoneThe barbiturate, primidone, decreases the effect of metronidazole.
Quinidine barbiturateThe barbiturate, quinidine barbiturate, decreases the effect of metronidazole.
SecobarbitalThe barbiturate, secobarbital, decreases the effect of metronidazole.
TacrolimusMetronidazole increases the levels/toxicity of tacrolimus
TalbutalThe barbiturate, talbutal, decreases the effect of metronidazole.
TamsulosinMetronidazole, 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.
TolterodineMetronidazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
TramadolMetronidazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
TrazodoneThe 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.
WarfarinMetronidazole 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

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: binder

Components

Name UniProt ID Details

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

Kind: protein

Organism: Helicobacter pylori (strain ATCC 700392 / 26695)

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Oxygen-insensitive NADPH nitroreductase O25608 Details

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. Iron hydrogenase 1

Kind: protein

Organism: Clostridium pasteurianum

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Iron hydrogenase 1 P29166 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

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
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:24