Metronidazole

Template:Short description Template:Use dmy dates Template:Cs1 config Template:Main other {{#invoke:Infobox|infobox}}Template:Template other{{#invoke:TemplatePar |check |template=Template:Infobox_drug |all= |opt= pronounce= pronounce_ref= pronounce_comment= ATC_prefix= ATC_suffix= ATC_supplemental= ATCvet= biosimilars= CAS_number_Ref= CAS_number= CAS_supplemental= ChEBI= ChEBI_Ref= ChEMBL_Ref= ChEMBL= ChemSpiderID= ChemSpiderID_Ref= chirality= class= container_only= DailyMedID= data_page= DrugBank_Ref= DrugBank= Drugs.com= duration_of_action= INN= INN_EMA= IUPAC_name= IUPHAR_ligand= KEGG_Ref= KEGG= MedlinePlus= NIAID_ChemDB= PDB_ligand= PubChemSubstance= PubChem= StdInChIKey_Ref= StdInChIKey= StdInChI_Ref= StdInChI_comment= StdInChI= UNII_Ref= UNII= DTXSID= Verifiedfields= Watchedfields= addiction_liability= alt2= altL= altR= alt= bioavailability= boiling_high= boiling_notes= boiling_point= captionLR= caption= caption2= charge= chemical_formula= chemical_formula_ref= chemical_formula_comment= class1= class2= class3= class4= class5= class6= component1= component2= component3= component4= component5= component6= density= density_notes= dependency_liability= drug_name= elimination_half-life= engvar= excretion= image2= imageL= imageR= image= image_class= image_class2= image_classL= image_classR= Jmol= legal_AU= legal_BR= legal_CA= legal_DE= legal_EU= legal_NZ= legal_UK= legal_UN= legal_US= legal_AU_comment= legal_BR_comment= legal_CA_comment= legal_DE_comment= legal_UK_comment= legal_NZ_comment= legal_US_comment= legal_UN_comment= legal_EU_comment= legal_status= licence_CA= licence_EU= licence_US= license_CA= license_EU= license_US= mab_type= melting_high= melting_notes= melting_point= metabolism= metabolites= molecular_weight= molecular_weight_round= molecular_weight_unit= molecular_weight_ref= molecular_weight_comment= onset= pregnancy_AU= pregnancy_AU_comment= pregnancy_category= protein_bound= routes_of_administration= SMILES= smiles= solubility= sol_units= source= specific_rotation= synonyms= target= tradename= type= vaccine_type= verifiedrevid= width2= widthL= widthR= width= AAN= BAN= JAN= USAN= source_tissues= target_tissues= receptors= agonists= antagonists= precursor= biosynthesis= gt_target_gene= gt_vector= gt_nucleic_acid_type= gt_editing_method= gt_delivery_method= sec_combustion= Ac=Ag=Al=Am=Ar=As=At=Au=B=Ba=Be=Bh=Bi=Bk=Br=C=Ca=Cd=Ce=Cf=Cl=Cm=Cn=Co=Cr=Cs=Cu= D=Db=Ds=Dy=Er=Es=Eu=F=Fe=Fl=Fm=Fr=Ga=Gd=Ge=H=He=Hf=Hg=Ho=Hs=I=In=Ir=K=Kr=La=Li=Lr=Lu=Lv= Mc=Md=Mg=Mn=Mo=Mt=N=Na=Nb=Nd=Ne=Nh=Ni=No=Np=O=Og=Os=P=Pa=Pb=Pd=Pm=Po=Pr=Pt=Pu=Ra=Rb=Re=Rf=Rg=Rh=Rn=Ru=S=Sb=Sc=Se=Sg=Si=Sm=Sn=Sr=Ta=Tb=Tc=Te=Th=Ti=Tl=Tm=Ts=U=V=W=Xe=Y=Yb=Zn=Zr= index_label= index2_label= index_comment= index2_comment= CAS_number2= CAS_supplemental2= ATC_prefix2= ATC_suffix2= ATC_supplemental2= PubChem2= PubChemSubstance2= IUPHAR_ligand2= DrugBank2= ChemSpiderID2= UNII2= KEGG2= ChEBI2= ChEMBL2= PDB_ligand2= NIAID_ChemDB2= SMILES2= smiles2= StdInChI2= StdInChIKey2= CAS_number2_Ref= ChEBI2_Ref= ChEMBL2_Ref= ChemSpiderID2_Ref= DrugBank2_Ref= KEGG2_Ref= StdInChI2_Ref= StdInChIKey2_Ref= UNII2_Ref= DTXSID2= QID= QID2=PLLR= pregnancy_US= pregnancy_US_comment= |cat=Pages using infobox drug with unknown parameters |format=0|errNS=0

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| _datapage = Metronidazole (data page) | _vaccine_target={{#ifeq: | vaccine | | _type_not_vaccine }} | _legal_all=S4Rx-onlyPOMRx-only | _ATC_prefix_supplemental=A01Template:ATC, Template:ATC, Template:ATC, Template:ATC, Template:ATCvet | _has_EMA_link = | CAS_number=443-48-1 | PubChem=4173 | ChemSpiderID=4029 | ChEBI=6909 | ChEMBL=137 | DrugBank=DB00916 | KEGG=D00409 | _hasInChI_or_Key={{#if:1S/C6H9N3O3/c1-5-7-4-6(9(11)12)8(5)2-3-10/h4,10H,2-3H2,1H3VAOCPAMSLUNLGC-UHFFFAOYSA-N |yes}} | UNII=140QMO216E | _hasJmol02 = |_hasMultipleCASnumbers = |_hasMultiplePubChemCIDs = |_hasMultipleChEBIs =

| _countSecondIDs={{#invoke:ParameterCount |main |CAS_number2 |ATC_prefix2 |PubChem2 |PubChemStructure2 |IUPHAR_ligand2 |DrugBank2 |ChemSpiderID2 |UNII2 |KEGG2 |ChEBI2 |ChEMBL2 |PDB_ligand2 |NIAID_ChemDB2 |SMILES2 |smiles2 |StdInChI2 |StdInChIKey2 |DTXCID2}} | _countIndexlabels={{#invoke:ParameterCount |main |index_label |index2_label}} | _trackListSortletter= |QID = |QID2 = |Verifiedfields= |Watchedfields=changed |verifiedrevid=699169263}} Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication.<ref name=AHFS2015/> It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis.<ref name=AHFS2015/> It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis.<ref name=AHFS2015/> It is an option for a first episode of mild-to-moderate Clostridioides difficile colitis if vancomycin or fidaxomicin is unavailable.<ref name=AHFS2015/><ref name="pmid29462280">Template:Cite journal</ref> Metronidazole is available orally (by mouth), as a cream or gel, and by slow intravenous infusion (injection into a vein).<ref name="AHFS2015">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="NIH">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Common side effects include nausea, a metallic taste, loss of appetite, and headaches.<ref name=AHFS2015/> Occasionally seizures or allergies to the medication may occur.<ref name=AHFS2015/> Some state that metronidazole should not be used in early pregnancy, while others state doses for trichomoniasis are safe.<ref name=Preg2017/>Template:Weasel inline Metronidazole is generally considered compatible with breastfeeding.<ref name="Preg2017">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="SPS - Specialist Pharmacy Service">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Metronidazole began to be commercially used in 1960 in France.<ref name="Corey-2013">Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO23rd">Template:Cite book</ref> It is available in most areas of the world.<ref name="Trichomoniasis treatment in women-2003">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2022, it was the 133rd most commonly prescribed medication in the United States, with more than 4Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

File:Metronidazole Aurobindo tube.jpg

A tube of metronidazole cream

Metronidazole has activity against some protozoans and most anaerobic bacteria (both Gram-negative and Gram-positive classes) but not the aerobic bacteria.<ref name="pmid9360057">Template:Cite journal</ref><ref name="pmid20067388">Template:Cite journal</ref>

Metronidazole is primarily used to treat: bacterial vaginosis, pelvic inflammatory disease (along with other antibacterials like ceftriaxone), pseudomembranous colitis, aspiration pneumonia, rosacea (topical), fungating wounds (topical), intra-abdominal infections, lung abscess, periodontal disease, amoebiasis, oral infections, giardiasis, trichomoniasis, and infections caused by susceptible anaerobic organisms such as Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus, and Prevotella species.<ref name = AMH/> It is also often used to eradicate Helicobacter pylori along with other drugs and to prevent infection in people recovering from surgery.<ref name = AMH/>

Metronidazole is bitter and so the liquid suspension contains metronidazole benzoate. This may require hydrolysis in the gastrointestinal tract and some sources speculate that it may be unsuitable in people with diarrhea or feeding-tubes in the duodenum or jejunum.<ref name="Geoghegan-2017">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Dickman-2012">Template:Cite book</ref>

Bacterial vaginosis

Drugs of choice for the treatment of bacterial vaginosis include metronidazole and clindamycin.<ref name="pmid10028110">Template:Cite journal</ref>

An effective treatment option for mixed infectious vaginitis is a combination of clotrimazole and metronidazole.<ref name="pmid37773671">Template:Cite journal</ref>

Trichomoniasis

The 5-nitroimidazole drugs (metronidazole and tinidazole) are the mainstay of treatment for infection with Trichomonas vaginalis. Treatment for both the infected patient and the patient's sexual partner is recommended, even if asymptomatic. Therapy other than 5-nitroimidazole drugs is also an option, but cure rates are much lower.<ref name="pmid9132982">Template:Cite journal</ref>

Giardiasis

Oral metronidazole is a treatment option for giardiasis, however, the increasing incidence of nitroimidazole resistance is leading to the increased use of other compound classes.<ref name="pmid26258002">Template:Cite journal</ref>

Dracunculus

In the case of Dracunculus medinensis (Guinea worm), metronidazole merely facilitates worm extraction rather than killing the worm.<ref name=AHFS2015/>

C. difficile colitis

Initial antibiotic therapy for less-severe Clostridioides difficile infection colitis (pseudomembranous colitis) consists of metronidazole, vancomycin, or fidaxomicin by mouth.<ref name="pmid29462280"/> In 2017, the IDSA generally recommended vancomycin and fidaxomicin over metronidazole.<ref name="pmid29462280"/> Vancomycin by mouth has been shown to be more effective in treating people with severe C. difficile colitis.<ref name="pmid17599306">Template:Cite journal</ref>

E. histolytica

Entamoeba histolytica invasive amebiasis is treated with metronidazole for eradication, in combination with diloxanide to prevent recurrence.<ref name="Ryan-2018">Template:Cite book</ref> Although it is generally a standard treatment it is associated with some side effects.<ref name="pmid32356312">Template:Cite journal</ref>

Preterm births

Metronidazole has also been used in women to prevent preterm birth associated with bacterial vaginosis, amongst other risk factors including the presence of cervicovaginal fetal fibronectin (fFN). Metronidazole was ineffective in preventing preterm delivery in high-risk pregnant women (selected by history and a positive fFN test) and, conversely, the incidence of preterm delivery was found to be higher in women treated with metronidazole.<ref name="pmid16398774">Template:Cite journal</ref>

Hypoxic radiosensitizer

In addition to its anti-biotic properties, attempts were also made to use a possible radiation-sensitizing effect of metronidazole in the context of radiation therapy against hypoxic tumors.<ref name="pmid6884824">Template:Cite journal</ref> However, the neurotoxic side effects occurring at the required dosages have prevented the widespread use of metronidazole as an adjuvant agent in radiation therapy.<ref name="Sarna_2013">Template:Cite journal</ref> However, other nitroimidazoles derived from metronidazole such as nimorazole with reduced electron affinity showed less serious neuronal side effects and have found their way into radio-onological practice for head and neck tumors in some countries.<ref name="Overgaard_1998">Template:Cite journal</ref>

Perioral dermatitis

Canadian Family Physician has recommended topical metronidazole as a third-line treatment for the perioral dermatitis either along with or without oral tetracycline or oral erythromycin as first and second line treatment respectively.<ref name="pmid15856972">Template:Cite journal</ref>

Adverse effects

Common adverse drug reactions (≥1% of those treated with the drug) associated with systemic metronidazole therapy include: nausea, diarrhea, weight loss, abdominal pain, vomiting, headache, dizziness, and metallic taste in the mouth. Intravenous administration is commonly associated with thrombophlebitis. Infrequent adverse effects include: hypersensitivity reactions (rash, itch, flushing, fever), headache, dizziness, vomiting, glossitis, stomatitis, dark urine, and paraesthesia.<ref name="AMH">Template:Cite book</ref> High doses and long-term systemic treatment with metronidazole are associated with the development of leucopenia, neutropenia, increased risk of peripheral neuropathy, and central nervous system toxicity.<ref name=AMH/> Common adverse drug reaction associated with topical metronidazole therapy include local redness, dryness and skin irritation; and eye watering (if applied near eyes).<ref name=AMH/><ref name="Drugs.com SFX">Template:Drugs.com</ref> Metronidazole has been associated with cancer in animal studies.<ref name="Flagyl metronidazole tablets label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Failed verification In rare cases, it can also cause temporary hearing loss that reverses after cessation of the treatment.<ref name="pmid10474673">Template:Cite journal</ref><ref name="pmid7986915">Template:Cite journal</ref>

Some evidence from studies in rats indicates the possibility it may contribute to serotonin syndrome, although no case reports documenting this have been published to date.<ref name="pmid17963129"/><ref name="pmid18971895">Template:Cite journal</ref>

Mutagenesis and carcinogenesis

In 2016 metronidazole was listed by the U.S. National Toxicology Program (NTP) as reasonably anticipated to be a human carcinogen.<ref name="National Toxicology Program (NTP)-2016"/> Although some of the testing methods have been questioned, oral exposure has been shown to cause cancer in experimental animals and has also demonstrated some mutagenic effects in bacterial cultures.<ref name="National Toxicology Program (NTP)-2016"/><ref name = TGA/> The relationship between exposure to metronidazole and human cancer is unclear.<ref name="National Toxicology Program (NTP)-2016"/><ref name="pmid12052431">Template:Cite journal</ref> One study <ref name="pmid3339906">Template:Cite journal</ref> found an excess in lung cancer among women (even after adjusting for smoking), while other studies <ref name="INCHEM2-1998">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="pmid9762949">Template:Cite journal</ref><ref name="pmid19585498">Template:Cite journal</ref> found either no increased risk, or a statistically insignificant risk.<ref name="National Toxicology Program (NTP)-2016">Template:Cite book</ref><ref name="Pfizer-Flagyl-375">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Metronidazole is listed as a possible carcinogen according to the World Health Organization (WHO) International Agency for Research on Cancer (IARC).<ref name="International Agency for Research on Cancer (IARC)-2019">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> A study in those with Crohn's disease also found chromosomal abnormalities in circulating lymphocytes in people treated with metronidazole.<ref name="TGA">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Stevens–Johnson syndrome

Metronidazole alone rarely causes Stevens–Johnson syndrome, but is reported to occur at high rates when combined with mebendazole.<ref name="pmid12604501">Template:Cite journal</ref>

Neurotoxicity

Several studies in the human<ref>Template:Cite journal</ref> and animal models have recorded the neurotoxicity of metronidazole. One possible mechanism underlying this toxicity is that metronidazole may interference with postsynaptic central monoaminergic neurotransmission and immunomodulation.<ref>Template:Cite journal</ref> Additionally other research suggests that the role of nitric oxide isoforms and inflammatory cytokines may also play a role.<ref>Template:Cite journal</ref>

Drug interactions

Alcohol

Consuming alcohol while taking metronidazole has been suspected in case reports to cause a disulfiram-like reaction with effects that can include nausea, vomiting, flushing of the skin, tachycardia, and shortness of breath.<ref name="pmid8947362">Template:Cite journal</ref> People are often advised not to drink alcohol during systemic metronidazole therapy and for at least 48 hours after completion of treatment.<ref name="AMH"/> However, some studies call into question the mechanism of the interaction of alcohol and metronidazole,<ref name="pmid4320226">Template:Cite journal</ref><ref name="pmid10676835"> Template:Cite journal</ref><ref name="pmid12022894">Template:Cite journal</ref> and a possible central toxic serotonin reaction for the alcohol intolerance is suggested.<ref name="pmid17963129">Template:Cite journal</ref> Metronidazole is also generally thought to inhibit the liver metabolism of propylene glycol (found in some foods, medicines, and in many electronic cigarette e-liquids), thus propylene glycol may potentially have similar interaction effects with metronidazole.Template:Medical citation needed

Other drug interactions

Metronidazole is a moderate inhibitor of the enzyme CYP2C9 belonging to the cytochrome P450 family. As a result, metronidazole may interact with medications metabolized by this enzyme.<ref name="Flockhart-2007">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="pmid25470432">Template:Cite journal</ref><ref name="pmid20698928">Template:Cite journal</ref> Examples of such medications are lomitapide and warfarin, to name a few.<ref name = MSR/>

Pharmacology

File:Metronidazole mechanism schematic 2.svg

Illustration of how metronidazole incorporates itself into anaerobic respiration.

Mechanism of action

Metronidazole is of the nitroimidazole class. It is a prodrug that inhibits nucleic acid synthesis by forming nitroso radicals, which disrupt the DNA of microbial cells.<ref name = MSR/><ref name="AC">Template:Cite book</ref> Metronidazole activates by receiving an electron from the reduced ferredoxin produced by pyruvate synthase (PFOR) in anaerobic organisms, equivalent to pyruvate dehydrogenase in aerobic organisms, thus turning into a highly reactive radical anion. After the radical loses the electron to its target, it recycles back to the unactivated form of metronidazole, ready to be activated again.<ref name="Brunton_2011">Template:Cite book</ref>

This function only occurs when metronidazole is partially reduced, and because oxygen competes with metronidazole for the electron, this reduction requires a local environment with low oxygen concentration that usually happens only in anaerobic bacteria and protozoans. Therefore, it has relatively little effect upon human cells or aerobic bacteria.<ref name="Eisenstein-2007"> Template:Cite book</ref> Elevation of oxygen level in the organism will decrease its rate of generating the activated metronidazole, but also increase the rate of recycling back to the unactivated metronidazole.<ref name="Brunton_2011" />

Pharmacokinetics

File:Hydroxymetronidazole.svg

Hydroxymetronidazole, the main metabolite

Oral metronidazole is approximately 80% bioavailable via the gut and peak blood plasma concentrations occur after one to two hours. Food may slow down absorption but does not diminish it. Of the circulating substance, about 20% is bound to plasma proteins. It penetrates well into tissues, the cerebrospinal fluid, the amniotic fluid and breast milk, as well as into abscess cavities.<ref name="AC" />

About 60% of the metronidazole is metabolized by oxidation to the main metabolite hydroxymetronidazole and a carboxylic acid derivative, and by glucuronidation. The metabolites show antibiotic and antiprotozoal activity in vitro.<ref name="AC" /> Metronidazole and its metabolites are mainly excreted via the kidneys (77%) and to a lesser extent via the faeces (14%).<ref name = MSR/><ref name = MD/> The biological half-life of metronidazole in healthy adults is eight hours, in infants during the first two months of their lives about 23 hours, and in premature babies up to 100 hours.<ref name="AC" />

The biological activity of hydroxymetronidazole is 30% to 65%, and the elimination half-life is longer than that of the parent compound.<ref name="pmid10384859">Template:Cite journal</ref> The serum half-life of hydroxymetronidazole after suppository was 10 hours, 19 hours after intravenous infusion, and 11 hours after a tablet.<ref name="pmid6588489">Template:Cite journal</ref>

Resistance

Resistance in parasites is found in T. vaginilis, and G. lamblia, but not E. histolytica, and two major methods are observed. The first method involves an impaired oxygen scavenging capability that increase the local concentration of oxygen, leading to the decreased activation and increased recycling of metronidazole. The second method is associated with lowered levels of pyruvate synthase and ferredoxin, the latter due to the lowered transcription of the ferredoxin gene. Strains employing the second method will still respond to a higher dosage of metronidazole.<ref name="Brunton_2011" />

Resistance in bacteria is documented in Bacteriodes spp. that resistant to nitroimidazoles including metronidazole. In the resistant strains, 5-nitroimidazole reductase is identified as the culprit that actively reduces metronidazole to inactive forms. Currently eleven types are identified which are encoded by nimA through nimK respectively. The gene is encoded either in the chromosome or the episome.<ref name="Brunton_2011" /><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Other mechanisms may include reduced drug activation, efflux pumps, altered redox potential and biofilm formation. In the recent years it is observed that the resistance to metronidazole is increasingly common, complicating its clinical effectiveness.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>Template:Clarify

History

The drug was initially developed by Rhône-Poulenc in the 1950s<ref name="pmid25557515">Template:Cite journal</ref> and licensed to G.D. Searle.<ref name="Leagle">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Searle was acquired by Pfizer in 2003.<ref name="Pfizer-2">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The original patent expired in 1982, but evergreening reformulation occurred thereafter.<ref name="pmid30799664">Template:Cite journal</ref>

Brand name

In India, it is sold under the brand name Metrogyl and Flagyl.<ref name="Medical Dialogues">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In Bangladesh, it is available as Amodis, Amotrex, Dirozyl, Filmet, Flagyl, Flamyd, Metra, Metrodol, Metryl, etc.<ref name="Medex">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In Pakistan, it is sold under the brand name of Flagyl and Metrozine.Template:Citation needed In the United States it is sold under the brand name Noritate.<ref name="RxList">Template:Cite news</ref>

Synthesis

2-Methylimidazole (1) may be prepared via the Debus-Radziszewski imidazole synthesis, or from ethylenediamine and acetic acid, followed by treatment with lime, then Raney nickel. 2-Methylimidazole is nitrated to give 2-methyl-4(5)-nitroimidazole (2), which is in turn alkylated with ethylene oxide or 2-chloroethanol to give metronidazole (3):<ref name="Ebel">Template:Ullmann</ref><ref name="Actor">Template:Ullmann</ref><ref name="Kraft-1989">Template:Cite journal</ref>

File:Synthesis of metronidazole.png

Research

Metronidazole is researched for its anti-inflammatory and immunomodulatory properties. Studies have shown that metronidazole can decrease the production of reactive oxygen species (ROS) and nitric oxide by activated immune cells, such as macrophages and neutrophils. Metronidazole's immunomodulatory properties are thought to be related to its ability to decrease the activation of nuclear factor-kappa B (NF-κB), a transcription factor that regulates the expression of pro-inflammatory cytokines, including chemokines, and adhesion molecules. Cytokines are small proteins that are secreted by immune cells and play a key role in the immune response.<ref name="pmid10767254">Template:Cite journal</ref> Chemokines are a type of cytokines that act as chemoattractants, meaning they attract and guide immune cells to specific sites in the body where they are needed.<ref name="pmid26490276">Template:Cite journal</ref> Cell adhesion molecules play an important role in the immune response by facilitating the interaction between immune cells and other cells in the body, such as endothelial cells, which form the lining of blood vessels.<ref name="pmid9150551">Template:Cite journal</ref> By inhibiting NF-κB activation, metronidazole can reduce the production of pro-inflammatory cytokines, such as TNF-alpha, IL-6, and IL-1β.<ref name="pmid20399284">Template:Cite journal</ref>

Metronidazole has been studied in various immunological disorders, including inflammatory bowel disease, periodontitis, and rosacea. In these conditions, metronidazole has been suspected to have anti-inflammatory and immunomodulatory effects that could be beneficial in the treatment of these conditions.<ref name="pmid37295025">Template:Cite journal</ref> Despite the success in treating rosacea with metronidazole,<ref name="pmid37550898">Template:Cite journal</ref><ref name="pmid37591279">Template:Cite journal</ref><ref name="pmid36478427">Template:Cite journal</ref><ref name="pmid36177741">Template:Cite journal</ref><ref name="pmid36330970">Template:Cite journal</ref> the exact mechanism of why metronidazole in rosacea is efficient is not precisely known, i.e., which properties of metronidazole help treat rosacea: antibacterial or immunomodulatory or both, or other mechanism is involved.<ref name="pmid32362310">Template:Cite journal</ref><ref name="pmid18182250">Template:Cite journal</ref> Increased ROS production in rosacea is thought to contribute to the inflammatory process and skin damage, so metronidazole's ability to decrease ROS may explain the mechanism of action in this disease, but this remains speculation.<ref name="pmid15499754">Template:Cite journal</ref><ref name="pmid17725855">Template:Cite journal</ref>

Metronidazole is also researched as a potential anti-inflammatory agent in periodontitis treatment.<ref name="pmid38613247">Template:Cite journal</ref>

Veterinary use

Metronidazole is used to treat infections of Giardia in dogs, cats, and other companion animals, but it does not reliably clear infection with this organism and is being supplanted by fenbendazole for this purpose in dogs and cats.<ref name="pmid7978640">Template:Cite journal</ref> It is also used for the management of chronic inflammatory bowel disease, gastrointestinal infections, periodontal disease, and systemic infections in cats and dogs.<ref name="Hoskins-2001">Template:Cite news</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Another common usage is the treatment of systemic and/or gastrointestinal clostridial infections in horses. Metronidazole is used in the aquarium hobby to treat ornamental fish and as a broad-spectrum treatment for bacterial and protozoan infections in reptiles and amphibians. In general, the veterinary community may use metronidazole for any potentially susceptible anaerobic infection. The U.S. Food and Drug Administration (FDA) suggests it only be used when necessary because it has been shown to be carcinogenic in mice and rats, as well as to prevent antimicrobial resistance.<ref name="Plumb-2008">Template:Cite book</ref><ref name="Drugs.com">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

The appropriate dosage of metronidazole varies based on the animal species, the condition being treated and the specific formulation of the product.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

External links

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