LOMEFLOXACIN HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H19F2N3O3.ClH
Molecular Weight	387.809
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(N3CCNC(C)C3)C(F)=C12

InChI

InChIKey=KXEBLAPZMOQCKO-UHFFFAOYSA-N

InChI=1S/C17H19F2N3O3.ClH/c1-3-21-8-11(17(24)25)16(23)10-6-12(18)15(13(19)14(10)21)22-5-4-20-9(2)7-22;/h6,8-9,20H,3-5,7H2,1-2H3,(H,24,25);1H

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/20013s015lbl.pdf | http://home.intekom.com/pharm/adcock/okacyned.html

Lomefloxacin hydrochloride (marketed under the following brand names in English speaking countries Maxaquin, Okacyn, Uniquin) is a fluoroquinolone antibiotic used to treat bacterial infections. It is used to treat chronic bronchitis, as well as complicated and uncomplicated urinary tract infections. It is also used as a prophylactic or preventative treatment to prevent urinary tract infections in patients undergoing transrectal or transurethral surgical procedures. Flouroquinolones such as lomefloxacin possess excellent activity against gram-negative aerobic bacteria such as E.coli and Neisseria gonorrhoea as well as gram-positive bacteria including S. pneumoniae and Staphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter. Lomefloxacin is a bactericidal fluoroquinolone agent with activity against a wide range of gram-negative and gram-positive organisms. The bactericidal action of lomefloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial DNA gyrase 66 Target ID: CHEMBL2311224 Sources: http://home.intekom.com/pharm/adcock/okacyned.html \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/20013s015lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/10621934 \| https://www.ncbi.nlm.nih.gov/pubmed/10590273	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Chronic bronchitis 51 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/20013s015lbl.pdf	Curative	Approved 8429	MAXAQUIN Approved Use Maxaquin (lomefloxacin HCl) film-coated tablets are indicated for the treatment of adults with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below: (See Dosage and Administration for specific dosing recommendations.) LOWER RESPIRATORY TRACT Acute Bacterial Exacerbation of Chronic Bronchitis caused by Haemophilus influenzae or Moraxella catarrhalis.* NOTE: MAXAQUIN IS NOT INDICATED FOR THE EMPIRIC TREATMENT OF ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS WHEN IT IS PROBABLE THAT S PNEUMONIAE IS A CAUSATIVE PATHOGEN. S PNEUMONIAE EXHIBITS IN VITRO RESISTANCE TO LOMEFLOXACIN, AND THE SAFETY AND EFFICACY OF LOMEFLOXACIN IN THE TREATMENT OF PATIENTS WITH ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS CAUSED BY S PNEUMONIAE HAVE NOT BEEN DEMONSTRATED. IF LOMEFLOXACIN IS TO BE PRESCRIBED FOR GRAMSTAIN–GUIDED EMPIRIC THERAPY OF ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS, IT SHOULD BE USED ONLY IF SPUTUM GRAM STAIN DEMONSTRATES AN ADEQUATE QUALITY OF SPECIMEN (> 25 PMNs/LPF) AND THERE IS BOTH A PREDOMINANCE OF GRAM-NEGATIVE MICROORGANISMS AND NOT A PREDOMINANCE OF GRAM-POSITIVE MICROORGANISMS. URINARY TRACT Uncomplicated Urinary Tract Infections (cystitis) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Staphylococcus saprophyticus. (See DOSAGE AND ADMINISTRATION and CLINICAL STUDIES— UNCOMPLICATED CYSTITIS.) Complicated Urinary Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Citrobacter diversus,* or Enterobacter cloacae.* NOTE: In clinical trials with patients experiencing complicated urinary tract infections (UTIs) due to P aeruginosa, 12 of 16 patients had the microorganism eradicated from the urine after therapy with lomefloxacin. None of the patients had concomitant bacteremia. Serum levels of lomefloxacin do not reliably exceed the MIC of Pseudomonas isolates. THE SAFETY AND EFFICACY OF LOMEFLOXACIN IN TREATING PATIENTS WITH PSEUDOMONAS BACTEREMIA HAVE NOT BEEN ESTABLISHED. Prevention / prophylaxis: Maxaquin is indicated preoperatively for the prevention of infection in the following situations: •Transrectal prostate biopsy: to reduce the incidence of urinary tract infection, in the early and late postoperative periods (3–5 days and 3–4 weeks postsurgery). •Transurethral surgical procedures: to reduce the incidence of urinary tract infection in the early postoperative period (3–5 days postsurgery). Launch Date 1992
Uncomplicated urinary tract infections 7 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/20013s015lbl.pdf	Curative	Approved 8429	MAXAQUIN Approved Use Maxaquin (lomefloxacin HCl) film-coated tablets are indicated for the treatment of adults with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below: (See Dosage and Administration for specific dosing recommendations.) LOWER RESPIRATORY TRACT Acute Bacterial Exacerbation of Chronic Bronchitis caused by Haemophilus influenzae or Moraxella catarrhalis.* NOTE: MAXAQUIN IS NOT INDICATED FOR THE EMPIRIC TREATMENT OF ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS WHEN IT IS PROBABLE THAT S PNEUMONIAE IS A CAUSATIVE PATHOGEN. S PNEUMONIAE EXHIBITS IN VITRO RESISTANCE TO LOMEFLOXACIN, AND THE SAFETY AND EFFICACY OF LOMEFLOXACIN IN THE TREATMENT OF PATIENTS WITH ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS CAUSED BY S PNEUMONIAE HAVE NOT BEEN DEMONSTRATED. IF LOMEFLOXACIN IS TO BE PRESCRIBED FOR GRAMSTAIN–GUIDED EMPIRIC THERAPY OF ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS, IT SHOULD BE USED ONLY IF SPUTUM GRAM STAIN DEMONSTRATES AN ADEQUATE QUALITY OF SPECIMEN (> 25 PMNs/LPF) AND THERE IS BOTH A PREDOMINANCE OF GRAM-NEGATIVE MICROORGANISMS AND NOT A PREDOMINANCE OF GRAM-POSITIVE MICROORGANISMS. URINARY TRACT Uncomplicated Urinary Tract Infections (cystitis) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Staphylococcus saprophyticus. (See DOSAGE AND ADMINISTRATION and CLINICAL STUDIES— UNCOMPLICATED CYSTITIS.) Complicated Urinary Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Citrobacter diversus,* or Enterobacter cloacae.* NOTE: In clinical trials with patients experiencing complicated urinary tract infections (UTIs) due to P aeruginosa, 12 of 16 patients had the microorganism eradicated from the urine after therapy with lomefloxacin. None of the patients had concomitant bacteremia. Serum levels of lomefloxacin do not reliably exceed the MIC of Pseudomonas isolates. THE SAFETY AND EFFICACY OF LOMEFLOXACIN IN TREATING PATIENTS WITH PSEUDOMONAS BACTEREMIA HAVE NOT BEEN ESTABLISHED. Prevention / prophylaxis: Maxaquin is indicated preoperatively for the prevention of infection in the following situations: •Transrectal prostate biopsy: to reduce the incidence of urinary tract infection, in the early and late postoperative periods (3–5 days and 3–4 weeks postsurgery). •Transurethral surgical procedures: to reduce the incidence of urinary tract infection in the early postoperative period (3–5 days postsurgery). Launch Date 1992
Bacterial conjunctivitis 34 Sources: http://home.intekom.com/pharm/adcock/okacyned.html	Curative	Approved 8429	OKACYN Approved Use Bacterial conjuctivitis due to susceptible organisms. Launch Date 2000

C_max

Value	Dose	Co-administered	Analyte	Population
2.8 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/20013s015lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LOMEFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
25.9 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/20013s015lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LOMEFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.75 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/20013s015lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LOMEFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
800 mg single, oral Highest studied dose Dose: 800 mg Route: oral Route: single Dose: 800 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3214495/	healthy, 21 - 24 years n = 5 Health Status: healthy Age Group: 21 - 24 years Sex: M Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/3214495/	Sources: https://pubmed.ncbi.nlm.nih.gov/3214495/
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://sci-hub.do/10.1016/s0090-4295(97)00708-5	unhealthy, 22–87 years n = 165 Health Status: unhealthy Condition: urinary tract infections Age Group: 22–87 years Sex: M+F Population Size: 165 Sources: https://sci-hub.do/10.1016/s0090-4295(97)00708-5	Disc. AE: Gastrointestinal disorders, Herpes labialis... AEs leading to discontinuation/dose reduction: Gastrointestinal disorders (14 patients) Herpes labialis (1 patient) Sources: https://sci-hub.do/10.1016/s0090-4295(97)00708-5

AEs

AE	Significance	Dose	Population
Herpes labialis	1 patient Disc. AE	400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://sci-hub.do/10.1016/s0090-4295(97)00708-5	unhealthy, 22–87 years n = 165 Health Status: unhealthy Condition: urinary tract infections Age Group: 22–87 years Sex: M+F Population Size: 165 Sources: https://sci-hub.do/10.1016/s0090-4295(97)00708-5
Gastrointestinal disorders	14 patients Disc. AE	400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://sci-hub.do/10.1016/s0090-4295(97)00708-5	unhealthy, 22–87 years n = 165 Health Status: unhealthy Condition: urinary tract infections Age Group: 22–87 years Sex: M+F Population Size: 165 Sources: https://sci-hub.do/10.1016/s0090-4295(97)00708-5

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478	UGT 192 OCT2 355

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30309202/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30309202/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30309202/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30309202/	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30309202/	no

Drug as victim

Target	Modality	Activity
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30309202/	no
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30309202/	no
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30309202/	no
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/20013s015lbl.pdf#page=	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/17027138/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:116278	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:116278
MolPort	MolPort-003-949-739	https://www.molport.com/shop/molecule-link/MolPort-003-949-739
eMolecules	566238	https://www.emolecules.com/cgi-bin/more?vid=566238

PubMed

Title	Date	PubMed
Prediction of quinolone activity against Mycobacterium avium by molecular topology and virtual computational screening.	2000 Oct	10991858
History of quinolones and their side effects.	2001	11549783
Unusual cause of hematuria.	2001	11150952
Analysis of fluoroquinolone-mediated photosensitization of 2'-deoxyguanosine, calf thymus and cellular DNA: determination of type-I, type-II and triplet-triplet energy transfer mechanism contribution.	2001 Mar	11281018
Is more than one quinolone needed in clinical practice?	2001 Sep	11573860
In vitro phototoxic properties of new 6-desfluoro and 6-fluoro-8-methylquinolones.	2002 Dec	12423651
Accumulation of ciprofloxacin and lomefloxacinin fluoroquinolone-resistant strains of Escherichia coli.	2002 Jan	11930654
[Lemofloxacin: antimicrobial ability and clinico-pharmacokinetic basis for use in urogenital infections].	2002 Jan-Feb	11877963
Lomefloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis.	2002 Jul	12127707
The expanding role of fluoroquinolones.	2002 Jul 8	12113871
[Study on the direct determination of lomefloxacin in urine by derivative-synchronous fluorescence].	2002 Jun	12938329
Possible involvement of P-glycoprotein in the biliary excretion of grepafloxacin.	2002 Mar	11906478
In vitro photochemical clastogenicity of quinolone antibacterial agents studied by a chromosomal aberration test with light irradiation.	2002 May 27	12034313
Determination of bioequivalence of lomefloxacin tablets using urinary excretion data.	2002 Nov 7	12408922
Determination of moxifloxacin in human plasma by liquid chromatography electrospray ionization tandem mass spectrometry.	2002 Nov 7	12408886
[Analysis of the response factors of different quinolones detected by evaporative light-scattering detector].	2003 Sep	14730921
Molecular responses to photogenotoxic stress induced by the antibiotic lomefloxacin in human skin cells: from DNA damage to apoptosis.	2003 Sep	12925221
Permeability classification of representative fluoroquinolones by a cell culture method.	2004 Apr 5	15760043
Vibrio vulnificus in Taiwan.	2004 Aug	15496235
Cotransport of macrolide and fluoroquinolones, a beneficial interaction reversing P-glycoprotein efflux.	2004 Nov-Dec	15543082
Clinical evaluation of ophthalmic lomefloxacin 0.3% in comparison with fortified cefazolin and gentamicin ophthalmic solutions in the treatment of presumed bacterial keratitis.	2004 Sep	16083168
[Comparative efficiency of treatment with moxyfloxacin and lomefloxacin for generalized murine tuberculosis caused by drug-resistant Mycobacterium strains].	2005	15881962
In vitro activity of fluoroquinolones against Mycobacterium tuberculosis.	2005 Apr	15920901
Evaluation of phototoxic and photoallergic potentials of 13 compounds by different in vitro and in vivo methods.	2005 Apr 4	15792876
Mutagenesis induced by 12 quinolone antibacterial agents in Escherichia coli WP2uvrA/pKM101.	2006 Apr	16171969

Patents

Sample Use Guides

In Vivo Use Guide

The recommended daily dose of Maxaquin (Lomefloxacin) is: Acute bacterial exacerbation of chronic bronchitis 400 mg qd 10 days 400 mg Uncomplicated cystitis in females caused by E coli 400 mg qd 3 days 400 mg

Route of Administration: Oral

In Vitro Use Guide

DNA synthesis in intact cells of E. cloacae, S. marcescens, and K. pneumoniae after 90 min of exposure was inhibited 90% (IC90) by 1 ug of lomefloxacin per ml. For E. coli, the IC50 and the IC90 of lomefloxacin were of the same order of magnitude, regardless of the growth stage of the culture, with IC90s of 0.12 and 0.37 ug/ml obtained for the early and late logarithmic phases, respectively.

Name

Type

Language

LOMEFLOXACIN HYDROCHLORIDE

Official Name

English

SC-47111

Code

English

LOMEFLOXACIN HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

LOMEFLOXACIN HCL

Common Name

English

NSC-758168

Code

English

LOMEFLOXACIN MONOHYDROCHLORIDE

Common Name

English

LOMEFLOXACIN HYDROCHLORIDE [JAN]

Common Name

English

LOMEFLOXACIN HYDROCHLORIDE [VANDF]

Common Name

English

LOMEFLOXACIN HYDROCHLORIDE [USAN]

Common Name

English

MAXAQUIN

Brand Name

English

LOMEFLOXACIN HYDROCHLORIDE [MART.]

Common Name

English

(±)-1-ETHYL-6,8-DIFLUORO-1,4-DIHYDRO-7-(3-METHYL-1-PIPERAZINYL)-4-OXO-3-QUINOLINECARBOXYLIC ACID, MONOHYDROCHLORIDE

Common Name

English

Lomefloxacin hydrochloride [WHO-DD]

Common Name

English

LOMEFLOXACIN MONOHYDROCHLORIDE [MI]

Common Name

English

3-QUINOLINECARBOXYLIC ACID, 1-ETHYL-6,8-DIFLUORO-1,4-DIHYDRO-7-(3-METHYL-1-PIPERAZINYL)-4-OXO-, MONOHYDROCHLORIDE, (±)-

Common Name

English

LOMEFLOXACIN (AS HYDROCHLORIDE)

Common Name

English

NY-198

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C795