BESIFLOXACIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H21ClFN3O3
Molecular Weight	393.84
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N[C@@H]1CCCCN(C1)C2=C(F)C=C3C(=O)C(=CN(C4CC4)C3=C2Cl)C(O)=O

InChI

InChIKey=QFFGVLORLPOAEC-SNVBAGLBSA-N

InChI=1S/C19H21ClFN3O3/c20-15-16-12(18(25)13(19(26)27)9-24(16)11-4-5-11)7-14(21)17(15)23-6-2-1-3-10(22)8-23/h7,9-11H,1-6,8,22H2,(H,26,27)/t10-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022308s003lbl.pdf

Besifloxacin (INN/USAN) is a fourth-generation fluoroquinolone antibiotic. The marketed compound is Besifloxacin hydrochloride. It was developed by SSP Co. Ltd., Japan, and designated SS734. SSP licensed U.S. and European rights to SS734 for ophthalmic use to InSite Vision Incorporated in 2000. InSite Vision developed an eye drop formulation (ISV-403) and conducted preliminary clinical trials before selling the product and all rights to Bausch & Lomb in 2003. Besifloxacin is indicated in the treatment of bacterial conjunctivitis caused by sensitive germs, as well as in the prevention of infectious complications in patients undergoing laser therapy for the treatment of cataracts. Besifloxacin inhibits bacterial DNA gyrase and topoisomerase IV and has a broad spectrum of bactericidal activity against strains commonly isolated from patients with bacterial conjunctivitis. In addition, some exploratory in vitro data suggest that Besifloxacin inhibits cytokine formation in human corneal epithelial cells and monocytes, but the relevance of this finding to therapeutic efficacy is unknown.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Topoisomerase IV 62 Target ID: CHEMBL2363076 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022308s000_PharmR.pdf	Inhibitor 8297
Bacterial DNA gyrase 66 Target ID: CHEMBL2311224 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022308s000_PharmR.pdf	Inhibitor 8297
Topoisomerase IV 62 Target ID: CHEMBL2363076 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022308s000_PharmR.pdf	Inhibitor 8297
Bacterial DNA gyrase 66 Target ID: CHEMBL2311224 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022308s000_PharmR.pdf	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Bacterial conjunctivitis 34 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022308s003lbl.pdf	Curative		Approved 8429	BESIVANCE Approved Use INDICATIONS AND USAGE. Besivance® (besifloxacin ophthalmic suspension) 0.6%, is a quinolone antimicrobial indicated for the treatment of bacterial conjunctivitis caused by susceptible isolates of the following bacteria: Aerococcus viridans , CDC coryneform group G, Corynebacterium pseudodiphtheriticum, Corynebacterium striatum, Haemophilus influenzae Moraxella catarrhalis, Pseudomonas aeruginosa , Moraxella lacunata, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus warneri, Streptococcus mitis group, Streptococcus oralis, Streptococcus pneumoniae, Streptococcus salivarius *Efficacy for this organism was studied in fewer than 10 infections. Launch Date 1.24338242E12

C_max

Value	Dose	Analyte	Population
610 μg/g EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19492955/	1 drop 4 times / day multiple, oral dose: 1 drop route of administration: Oral experiment type: MULTIPLE co-administered:	BESIFLOXACIN cornea	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.37 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022308s013lbl.pdf	1 drop single, ocular dose: 1 drop route of administration: Ocular experiment type: SINGLE co-administered:	BESIFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
56.4525 ng/ml Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01296191	1 drop 4 times / day multiple, ocular dose: 1 drop route of administration: ocular experiment type: multiple co-administered:	BESIFLOXACIN aqueous humor	Homo sapiens population: unhealthy age: sex: food status:

AUC

Value	Dose	Co-administered	Analyte	Population
1.232 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19492955/	1 drop 4 times / day multiple, oral dose: 1 drop route of administration: Oral experiment type: MULTIPLE co-administered:		BESIFLOXACIN cornea	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19492955/	1 drop 4 times / day multiple, oral dose: 1 drop route of administration: Oral experiment type: MULTIPLE co-administered:		BESIFLOXACIN cornea	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022308s013lbl.pdf	1 drop single, ocular dose: 1 drop route of administration: Ocular experiment type: SINGLE co-administered:		BESIFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 drop 3 times / day multiple, topical Recommended Dose: 1 drop, 3 times / day Route: topical Route: multiple Dose: 1 drop, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022308s013lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Bacterial conjunctivitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022308s013lbl.pdf Page: p.3	Disc. AE: Bacterial resistance... AEs leading to discontinuation/dose reduction: Bacterial resistance Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022308s013lbl.pdf Page: p.3

AEs

AE	Significance	Dose	Population
Bacterial resistance	Disc. AE	1 drop 3 times / day multiple, topical Recommended Dose: 1 drop, 3 times / day Route: topical Route: multiple Dose: 1 drop, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022308s013lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Bacterial conjunctivitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022308s013lbl.pdf Page: p.3

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 111	CYP 270	CYP 76

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 147	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022308s000_ClinPharmR.pdf#PAGE=26 Page: 26.0	unlikely
CYP 147	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022308s000_ClinPharmR.pdf#PAGE=26 Page: 26.0	unlikely

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022308s000_ClinPharmR.pdf#PAGE=26 Page: 26.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022308s000_PharmR.pdf#page=14 Page: 14.0

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific, Inc. (AKSCI)	Z6122	http://www.aksci.com/item_detail.php?cat=Z6122
Achemtek	0102-013346	http://www.achemtek.com/141388-76-3
ChemMol	30114323	http://www.chemmol.com/chemmol/30114323.html
ChemMol	49400296	http://www.chemmol.com/chemmol/49400296.html
Glentham Life Sciences	GA3299	http://www.glentham.com/products/product/GA3299/
Hairui	HR104538	http://www.hairuichem.com/en/product/141388-76-3.html
Matrix Scientific	120837	https://www.matrixscientific.com/120837.html
OChem	24101	http://www.ocheminc.com/index.php?act=psearch&pid=388B763
Selleck Chemicals	S5941	http://www.selleckchem.com/products/besifloxacin.html
Smolecule	S638463	https://www.smolecule.com/products/s638463
THE BioTek	bt-342289	https://www.thebiotek.com/product/others/bt-342289
iChemical	EBD24458	http://www.ichemical.com/chemicals/cas-141388-76-3

PubMed

Title	Date	PubMed
Nonclinical pharmacodynamics, pharmacokinetics, and safety of BOL-303224-A, a novel fluoroquinolone antimicrobial agent for topical ophthalmic use.	2007 Jun	17593008
Besifloxacin, a novel fluoroquinolone antimicrobial agent, exhibits potent inhibition of pro-inflammatory cytokines in human THP-1 monocytes.	2008 Jan	17965029
Quantitative determination of besifloxacin, a novel fluoroquinolone antimicrobial agent, in human tears by liquid chromatography-tandem mass spectrometry.	2008 May 1	18417430
Anti-inflammatory effects of besifloxacin, a novel fluoroquinolone, in primary human corneal epithelial cells.	2008 Nov	19085374
Besifloxacin ophthalmic suspension for bacterial conjunctivitis.	2009 Aug	19927224
Ocular pharmacokinetics of besifloxacin following topical administration to rabbits, monkeys, and humans.	2009 Aug	19492955
New drugs: golimumab, besifloxacin hydrochloride, and artemether/lumefantrine.	2009 Jul-Aug	19589772
Besifloxacin ophthalmic suspension 0.6% in patients with bacterial conjunctivitis: A multicenter, prospective, randomized, double-masked, vehicle-controlled, 5-day efficacy and safety study.	2009 Mar	19393842
Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli.	2009 Mar	19147516
Phase III efficacy and safety study of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis.	2009 May	19323612
Besifloxacin, a new ophthalmic fluoroquinolone for the treatment of bacterial conjunctivitis.	2009 Oct	19743941
Efficacy of besifloxacin in a rabbit model of methicillin-resistant Staphylococcus aureus keratitis.	2009 Oct	19724203
Efficacy and safety of besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% for treating bacterial conjunctivitis.	2009 Sep	19643483
Safety and tolerability of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis: data from six clinical and phase I safety studies.	2010	20629472
Besifloxacin ophthalmic suspension 0.6%.	2010	20030427
Efficacy of besifloxacin in an early treatment model of methicillin-resistant Staphylococcus aureus keratitis.	2010 Apr	20334537
Efficacy and safety of besifloxacin ophthalmic suspension 0.6% in children and adolescents with bacterial conjunctivitis: a post hoc, subgroup analysis of three randomized, double-masked, parallel-group, multicenter clinical trials.	2010 Apr 1	20218747
Penetration and effectiveness of prophylactic fluoroquinolones in experimental methicillin-sensitive or methicillin-resistant Staphylococcus aureus anterior chamber infections.	2010 Dec	21111321
New Drugs2010, PART 1.	2010 Feb	20083979
Bactericidal activity of besifloxacin against staphylococci, Streptococcus pneumoniae and Haemophilus influenzae.	2010 Jul	20435780
Comparative efficacy of besifloxacin and other fluoroquinolones in a prophylaxis model of penicillin-resistant Streptococcus pneumoniae rabbit endophthalmitis.	2010 Jun	20565309
Comparative effects of besifloxacin and other fluoroquinolones on corneal reepithelialization in the rabbit.	2010 Jun	20494783
Besifloxacin: a topical fluoroquinolone for the treatment of bacterial conjunctivitis.	2010 Mar	20399984
Ocular pharmacokinetics/pharmacodynamics of besifloxacin, moxifloxacin, and gatifloxacin following topical administration to pigmented rabbits.	2010 Oct	20874668
An anterior chamber toxicity study evaluating Besivance, AzaSite, and Ciprofloxacin.	2010 Oct	20678751
Aqueous penetration of moxifloxacin 0.5% ophthalmic solution and besifloxacin 0.6% ophthalmic suspension in cataract surgery patients.	2010 Sep	20692561
Besifloxacin ophthalmic suspension, 0.6%: a novel topical fluoroquinolone for bacterial conjunctivitis.	2012 Jun	22729919

Patents

Sample Use Guides

In Vivo Use Guide

Instill one drop in the affected eye(s) 3 times a day, four to twelve hours apart for 7 days.

Route of Administration: Topical

In Vitro Use Guide

HEK-293 cells stably transfected with HERG-1 cDNA were exposed to SS734 (Besifloxacin) in Tyrode’s solution. Patch-clamp techniques were used to monitor the HERG current in individual cells. The HERG tail current was inhibited by only 13% when cells were exposed to 100 mkM SS734.

Name

Type

Language

BESIFLOXACIN

Official Name

English

besifloxacin [INN]

Common Name

English

BESIFLOXACIN [VANDF]

Common Name

English

BESIFLOXACIN [MART.]

Common Name

English

3-QUINOLINECARBOXYLIC ACID, 7-((3R)-3-AMINOHEXAHYDRO-1H-AZEPIN-1-YL)-8-CHLORO-1-CYCLOPROPYL-6-FLUORO-1,4-DIHYDRO-4-OXO-

Common Name

English

(+)-7-((3R)-3-AMINOHEXAHYDRO-1H-AZEPIN-1-YL)-8-CHLORO-1-CYCLOPROPYL-6-FLUORO-4-OXO-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID

Systematic Name

English

BESIFLOXACINE

Common Name

English

BESIFLOXACIN [MI]

Common Name

English

Besifloxacin [WHO-DD]

Common Name

English

ISV-403

Code

English

Classification Tree Code System Code

WHO-VATC

QS01AE08