enoxacin

{{Drugbox

| verifiedrevid = 461093764

| IUPAC_name = 1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid

| image = Enoxacin.svg

| tradename =

| Drugs.com = {{drugs.com|monograph|oxistat}}

| MedlinePlus = a601013

| routes_of_administration = Oral

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 74011-58-8

| ATC_prefix = J01

| ATC_suffix = MA04

| PubChem = 3229

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00467

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 3116

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 325OGW249P

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D00310

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 157175

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 826

| C=15 | H=17 | F=1 | N=4 | O=3

| smiles = Fc1c(nc2c(c1)C(=O)C(\C(=O)O)=C/N2CC)N3CCNCC3

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C15H17FN4O3/c1-2-19-8-10(15(22)23)12(21)9-7-11(16)14(18-13(9)19)20-5-3-17-4-6-20/h7-8,17H,2-6H2,1H3,(H,22,23)

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = IDYZIJYBMGIQMJ-UHFFFAOYSA-N

| melting_point = 220

| melting_high = 224

}}

EnoxacinEnoxacin is sold under the following trade names: Almitil, Bactidan, Bactidron, Comprecin, Enoksetin, Enoxen, Enroxil, Enoxin, Enoxor, Flumark, Penetrex, Gyramid, Vinone. is an oral broad-spectrum fluoroquinolone antibacterial agent used in the treatment of urinary tract infections and gonorrhea. Insomnia is a common adverse effect.{{cite journal | vauthors = Rafalsky V, Andreeva I, Rjabkova E | title = Quinolones for uncomplicated acute cystitis in women | journal = The Cochrane Database of Systematic Reviews | volume = 2006 | issue = 3 | pages = CD003597 | date = July 2006 | pmid = 16856014 | pmc = 7003573 | doi = 10.1002/14651858.CD003597.pub2 | veditors = Rafalsky VV }}{{cite journal | vauthors = Mogabgab WJ | title = Recent developments in the treatment of sexually transmitted diseases | journal = The American Journal of Medicine | volume = 91 | issue = 6A | pages = 140S–144S | date = December 1991 | pmid = 1767802 | doi = 10.1016/0002-9343(91)90327-T }} It is no longer available in the United States.

Enoxacin may have cancer inhibiting effect.{{cite journal | vauthors = Jałbrzykowska K, Chrzanowska A, Roszkowski P, Struga M | title = The New Face of a Well-Known Antibiotic: A Review of the Anticancer Activity of Enoxacin and Its Derivatives | journal = Cancers | volume = 14 | issue = 13 | pages = 3056 | date = June 2022 | pmid = 35804828 | doi = 10.3390/cancers14133056 | doi-access = free | pmc = 9264829 }}

Mechanism of action

Quinolones and fluoroquinolones are bactericidal drugs, eradicating bacteria by interfering with DNA replication.

Like other fluoroquinolones, enoxacin functions by inhibiting bacterial DNA gyrase and topoisomerase IV. The inhibition of these enzymes prevents bacterial DNA replication, transcription, repair and recombination.{{cite journal | vauthors = Yoshida H, Nakamura M, Bogaki M, Ito H, Kojima T, Hattori H, Nakamura S | title = Mechanism of action of quinolones against Escherichia coli DNA gyrase | journal = Antimicrobial Agents and Chemotherapy | volume = 37 | issue = 4 | pages = 839–845 | date = April 1993 | pmid = 8388200 | pmc = 187778 | doi = 10.1128/aac.37.4.839 }}{{cite journal | vauthors = Wolfson JS, Hooper DC | title = The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro | journal = Antimicrobial Agents and Chemotherapy | volume = 28 | issue = 4 | pages = 581–586 | date = October 1985 | pmid = 3000292 | pmc = 180310 | doi = 10.1128/aac.28.4.581 }} Enoxacin inhibits the expression of the microRNA mir-34-5p, leading to an increase in the lifespan of the nematode C. elegans.{{cite journal | vauthors = Pinto S, Sato VN, De-Souza EA, Ferraz RC, Camara H, Pinca AP, Mazzotti DR, Lovci MT, Tonon G, Lopes-Ramos CM, Parmigiani RB, Wurtele M, Massirer KB, Mori MA | title = Enoxacin extends lifespan of C. elegans by inhibiting miR-34-5p and promoting mitohormesis | journal = Redox Biology | volume = 18 | pages = 84–92 | date = September 2018 | pmid = 29986212 | pmc = 6037660 | doi = 10.1016/j.redox.2018.06.006 }}

Enoxacin is active against many Gram-positive bacteria.Examples of Gram-positive bacteria include: Staphylococcus aureus, Staphylococcus epidermidis, Clostridium perfringens. The quinolone is also active against Gram-negative bacteria.Gram-negative bacteria include: Acinetobacter, Citrobacter, Campylobacter, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Serratia marcescens, Pseudomonas aeruginosa, Proteus mirabilis, Proteus vulgaris, Salmonella, Shigella flexneri.{{cite journal | vauthors = Chin NX, Neu HC | title = In vitro activity of enoxacin, a quinolone carboxylic acid, compared with those of norfloxacin, new beta-lactams, aminoglycosides, and trimethoprim | journal = Antimicrobial Agents and Chemotherapy | volume = 24 | issue = 5 | pages = 754–763 | date = November 1983 | pmid = 6229216 | pmc = 185938 | doi = 10.1128/aac.24.5.754 }}{{cite journal | vauthors = Wise R, Andrews JM, Danks G | title = In-vitro activity of enoxacin (CL-919), a new quinoline derivative, compared with that of other antimicrobial agents | journal = The Journal of Antimicrobial Chemotherapy | volume = 13 | issue = 3 | pages = 237–244 | date = March 1984 | pmid = 6586712 | doi = 10.1093/jac/13.3.237 }}

Pharmacokinetics

After oral administration enoxacin is rapidly and well absorbed from the gastrointestinal tract. The antibiotic is widely distributed throughout the body and in the different biological tissues. Tissue concentrations often exceed serum concentrations. The binding of enoxacin to serum proteins is 35 to 40%.

The serum elimination half-life, in subjects with normal renal function, is approximately 6 hours. Approximately 60% of an orally administered dose is excreted in the urine as unchanged drug within 24 hours.{{cite journal | vauthors = Wise R, Lockley R, Dent J, Webberly M | title = Pharmacokinetics and tissue penetration of enoxacin | journal = Antimicrobial Agents and Chemotherapy | volume = 26 | issue = 1 | pages = 17–19 | date = July 1984 | pmid = 6591851 | pmc = 179907 | doi = 10.1128/aac.26.1.17 }}{{cite journal | vauthors = Wise R, Lister D, McNulty CA, Griggs D, Andrews JM | title = The comparative pharmacokinetics and tissue penetration of four quinolones including intravenously administered enoxacin | journal = Infection | volume = 14 |issue = Suppl 3 | pages = S196–S202 | year = 1986 | pmid = 3463542 | doi = 10.1007/bf01667843 | s2cid = 21959049 }}

A small amount of a dose of drug administered is excreted in the bile.{{cite conference | vauthors = Flowerdew A, Walker E, Karran SJ | title= Evaluation of biliary pharmacokinetics of oral enoxacin, a new quinolone antibiotic. | conference = 14th International Congress of Chemotherapy | location = Kyoto | date = 1985 | page = 42 }} High concentrations of the fluoroquinolone are reached in the urinary tract and this fact ensures an antibacterial effect continued over time, particularly in this district.

Medical uses

Enoxacin can be used to treat a wide variety of infections, particularly gastroenteritis including infectious diarrhea, respiratory tract infections, gonorrhea{{cite journal | vauthors = van der Willigen AH, van der Hoek JC, Wagenvoort JH, van Vliet HJ, van Klingeren B, Schalla WO, Knapp JS, van Joost T, Michel MF, Stolz E | title = Comparative double-blind study of 200- and 400-mg enoxacin given orally in the treatment of acute uncomplicated urethral gonorrhea in males | journal = Antimicrobial Agents and Chemotherapy | volume = 31 | issue = 4 | pages = 535–538 | date = April 1987 | pmid = 3111354 | pmc = 174773 | doi = 10.1128/aac.31.4.535 }} and urinary tract infections.{{cite journal | vauthors = Huttunen M, Kunnas K, Saloranta P | title = Enoxacin treatment of urinary tract infections in elderly patients | journal = The Journal of Antimicrobial Chemotherapy | volume = 21 | issue = Suppl B | pages = 105–111 | date = February 1988 | pmid = 3162900 | doi = 10.1093/jac/21.suppl_b.105 }}{{cite journal | vauthors = Backhouse CI, Matthews JA | title = Single-dose enoxacin compared with 3-day treatment for urinary tract infection | journal = Antimicrobial Agents and Chemotherapy | volume = 33 | issue = 6 | pages = 877–880 | date = June 1989 | pmid = 2764538 | pmc = 284249 | doi = 10.1128/aac.33.6.877 }}

Adverse effects

Enoxacin, like other fluoroquinolones, is known to trigger seizures or lower the seizure threshold.{{cite journal | vauthors = De Sarro A, Zappalá M, Chimirri A, Grasso S, De Sarro GB | title = Quinolones potentiate cefazolin-induced seizures in DBA/2 mice | journal = Antimicrobial Agents and Chemotherapy | volume = 37 | issue = 7 | pages = 1497–1503 | date = July 1993 | pmid = 8395790 | pmc = 188001 | doi = 10.1128/aac.37.7.1497 }} The compound should not be administered to patients with epilepsy or a personal history of previous convulsive attacks as it may promote the onset of these disorders.{{cite journal | vauthors = Simpson KJ, Brodie MJ | title = Convulsions related to enoxacin | journal = Lancet | volume = 2 | issue = 8447 | pages = 161 | date = July 1985 | pmid = 2862357 | doi = 10.1016/s0140-6736(85)90270-3 | s2cid = 45528661 }}

Contraindications

Enoxacin is contraindicated in subjects with a history of hypersensitivity to the substance or any other member of the quinolone class, or any component of the medicine. Enoxacin, like other fluoroquinolones, can cause degenerative changes in weightbearing joints of young animals. The compound should only be used in children

when the expected benefits are outweigh the risks.{{cite journal | vauthors = Chalumeau M, Tonnelier S, D'Athis P, Tréluyer JM, Gendrel D, Bréart G, Pons G | title = Fluoroquinolone safety in pediatric patients: a prospective, multicenter, comparative cohort study in France | journal = Pediatrics | volume = 111 | issue = 6 Pt 1 | pages = e714–e719 | date = June 2003 | pmid = 12777590 | doi = 10.1542/peds.111.6.e714 | doi-access = free }}{{cite journal | title = The use of systemic fluoroquinolones | journal = Pediatrics | volume = 118 | issue = 3 | pages = 1287–1292 | date = September 2006 | pmid = 16951028 | doi = 10.1542/peds.2006-1722 | doi-access = free | author1 = Committee on Infectious Diseases }}

Interactions

Fenbufen: co-administration with some quinolones, including enoxacin may increase the risk of seizures. For this reason, concomitant administration of fenbufen and the quinolone should be avoided, as a precaution.{{cite journal | vauthors = Morita H, Maemura K, Sakai Y, Kaneda Y | title = [A case of convulsion, loss of consciousness and subsequent acute renal failure caused by enoxacin and fenbufen] | language = ja | journal = Nihon Naika Gakkai Zasshi. The Journal of the Japanese Society of Internal Medicine | volume = 77 | issue = 5 | pages = 744–745 | date = May 1988 | pmid = 3216153 | doi = 10.2169/naika.77.744 | doi-access = free }}{{cite journal | vauthors = Hara Y, Ally A, Suzuki T, Murayama S | title = [Effects of drugs on the convulsions induced by the combination of a new quinolone antimicrobial, enoxacin, and a nonsteroidal anti-inflammatory drug, fenbufen, in mice] | language = ja | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 100 | issue = 4 | pages = 301–305 | date = October 1992 | pmid = 1446880 | doi = 10.1254/fpj.100.301 | doi-access = free }}{{cite journal | vauthors = Masukawa T, Nakanishi K, Natsuki R | title = Role of nitric oxide in the convulsions following the coadministration of enoxacin with fenbufen in mice | journal = Japanese Journal of Pharmacology | volume = 76 | issue = 4 | pages = 425–429 | date = April 1998 | pmid = 9623721 | doi = 10.1254/jjp.76.425 | doi-access = free }}{{cite journal | vauthors = Masukawa T, Nakanishi K | title = Circadian variation in enoxacin-induced convulsions in mice coadministered with fenbufen | journal = Japanese Journal of Pharmacology | volume = 73 | issue = 2 | pages = 175–177 | date = February 1997 | pmid = 9074952 | doi = 10.1254/jjp.73.175 | doi-access = free }}
Theophylline: in patients treated concurrently with theophylline and enoxacin, concentrations of the methylxanthine in plasma arise due to a reduced metabolic clearance of theophylline.{{cite journal | vauthors = Wijnands WJ, van Herwaarden CL, Vree TB | title = Enoxacin raises plasma theophylline concentrations | journal = Lancet | volume = 2 | issue = 8394 | pages = 108–109 | date = July 1984 | pmid = 6145999 | doi = 10.1016/s0140-6736(84)90283-6 | s2cid = 22217064 }}{{cite journal | vauthors = Niki Y, Soejima R, Kawane H, Sumi M, Umeki S | title = New synthetic quinolone antibacterial agents and serum concentration of theophylline | journal = Chest | volume = 92 | issue = 4 | pages = 663–669 | date = October 1987 | pmid = 3477409 | doi = 10.1378/chest.92.4.663 | url = http://journal.publications.chestnet.org/article.aspx?volume=92&page=663 | url-status = dead | access-date = 2014-09-25 | archive-url = https://archive.today/20140925093247/http://journal.publications.chestnet.org/article.aspx?volume=92&page=663 | archive-date = 2014-09-25 }}{{cite journal | vauthors = Mizuki Y, Fujiwara I, Yamaguchi T, Sekine Y | title = Structure-related inhibitory effect of antimicrobial enoxacin and derivatives on theophylline metabolism by rat liver microsomes | journal = Antimicrobial Agents and Chemotherapy | volume = 40 | issue = 8 | pages = 1875–1880 | date = August 1996 | pmid = 8843297 | pmc = 163433 | doi = 10.1128/AAC.40.8.1875 }}{{cite journal | vauthors = Sano M, Kawakatsu K, Ohkita C, Yamamoto I, Takeyama M, Yamashina H, Goto M | title = Effects of enoxacin, ofloxacin and norfloxacin on theophylline disposition in humans | journal = European Journal of Clinical Pharmacology | volume = 35 | issue = 2 | pages = 161–165 | year = 1988 | pmid = 3191935 | doi = 10.1007/bf00609246 | s2cid = 1513011 }}
Ranitidine, sucralfate, antacids containing magnesium or aluminium, supplements containing calcium, iron, or zinc: co-administration with these substances can lead to therapeutic failure of the antibiotic due to decreased absorption by the intestinal tract. For example, magnesium or aluminium antacids turn enoxacin into insoluble salts that are not readily absorbed by the gastroenteric tract.{{cite journal | vauthors = Grasela TH, Schentag JJ, Sedman AJ, Wilton JH, Thomas DJ, Schultz RW, Lebsack ME, Kinkel AW | title = Inhibition of enoxacin absorption by antacids or ranitidine | journal = Antimicrobial Agents and Chemotherapy | volume = 33 | issue = 5 | pages = 615–617 | date = May 1989 | pmid = 2751276 | pmc = 172500 | doi = 10.1128/aac.33.5.615 }}{{cite journal | vauthors = Nix DE, Lebsack ME, Chapelsky M, Sedman AJ, Busch J, Norman A | title = Effect of oral antacids on disposition of intravenous enoxacin | journal = Antimicrobial Agents and Chemotherapy | volume = 37 | issue = 4 | pages = 775–777 | date = April 1993 | pmid = 8494374 | pmc = 187758 | doi = 10.1128/aac.37.4.775 }}{{cite journal | vauthors = Misiak PM, Eldon MA, Toothaker RD, Sedman AJ | title = Effects of oral cimetidine or ranitidine on the pharmacokinetics of intravenous enoxacin | journal = Journal of Clinical Pharmacology | volume = 33 | issue = 1 | pages = 53–56 | date = January 1993 | pmid = 8429114 | doi = 10.1002/j.1552-4604.1993.tb03903.x | s2cid = 35219055 }}