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Identification
NameBesifloxacin
Accession NumberDB06771
TypeSmall Molecule
GroupsApproved
Description

Besifloxacin is a fourth generation fluoroquinolone-type opthalmic antibiotic for the treatment of bacterial conjunctivitis. FDA approved on May 28, 2009.

Structure
Thumb
Synonyms
Besifloxacin
SS734
External Identifiers
  • BOL-303224-A
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Besivancesuspension6 mg/mLophthalmicBausch & Lomb Incorporated2009-05-28Not applicableUs
Besivancesuspension0.6 %ophthalmicBausch & Lomb Inc2010-01-27Not applicableCanada
Besivancesuspension6 mg/mLophthalmicPhysicians Total Care, Inc.2011-07-13Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Besifloxacin hydrochloride
Thumb
  • InChI Key: PMQBICKXAAKXAY-HNCPQSOCSA-N
  • Monoisotopic Mass: 429.102225204
  • Average Mass: 430.301
DBSALT000018
Categories
UNIIBFE2NBZ7NX
CAS number141388-76-3
WeightAverage: 393.84
Monoisotopic: 393.125547465
Chemical FormulaC19H21ClFN3O3
InChI KeyInChIKey=QFFGVLORLPOAEC-SNVBAGLBSA-N
InChI
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
IUPAC Name
7-[(3R)-3-aminoazepan-1-yl]-8-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
N[C@@H]1CCCCN(C1)C1=C(F)C=C2C(=O)C(=CN(C3CC3)C2=C1Cl)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at one or more positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassQuinoline carboxylic acids
Direct ParentQuinoline carboxylic acids
Alternative Parents
Substituents
  • Quinoline-3-carboxylic acid
  • Fluoroquinolone
  • Chloroquinoline
  • Dihydroquinolone
  • Aminoquinoline
  • Dihydroquinoline
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Dialkylarylamine
  • Fluorobenzene
  • Chlorobenzene
  • Azepane
  • Benzenoid
  • Pyridine
  • Aryl halide
  • Aryl fluoride
  • Aryl chloride
  • Heteroaromatic compound
  • Vinylogous amide
  • Cyclic alcohol
  • Tertiary amine
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationTreatment of bacterial conjunctivitis. Bacterial isolates that are susceptible to besifloxacin include: CDC coryneform group G; Corynebacterium pseudodiphtheriticum; Corynebacterium striatum; Haemophilus influenzae; Moraxella lacunata; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus hominis; Staphylococcus lugdunensis; Streptococcus mitis group; Streptococcus oralis; Streptococcus pneumoniae; Streptococcus salivarius*
PharmacodynamicsBesifloxacin tear concentrations were higher than MIC90 (minimum inhibitory concentration) values for common bacterial pathogens and sustained for 24 hours or longer. Mean residence time in the conjunctiva was 4.7 hours.
Mechanism of actionBesifloxacin is a bactericidal fluroquinolone-type antibiotic that inhibits bacterial enzymes, DNA gyrase and topoisomerase IV. By inhibiting DNA gyrase, DNA replication, transcription, and repair is impaired. By inhibiting topoisomerase IV, decatenation during cell devision is impaired. Inhibiting these two targets also slows down development of resistance.
Related Articles
AbsorptionAlthough ocular surface concentrations are high, average systemic concentrtions after three-times daily dosing was less than 0.5 ng/mL. This indicates that besifloxacin is not appreciably absorbed into the systemic and has a very low risk of systemic side effects.
Volume of distribution

Not absorbed into the systemic

Protein bindingNone
Metabolism

No appreciable metabolism

Route of eliminationN/A
Half lifeThe average elimination half-life of besifloxacin in plasma following multiple dosing was estimated to be 7 hours.
Clearance

N/A

ToxicityLD50, rat: >2000 mg/kg. The most common adverse reaction reported in 2% of patients treated with besifloxacin was conjunctival redness.
Affected organisms
  • Gram negative and gram positive bacteria
  • Pseudomonas aeruginosa
  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Staphylococcus aureus
  • Aerococcus viridans
  • Corynebacterium sp. G
  • Corynebacterium pseudodiphtheriticum
  • Corynebacterium striatum
  • Moraxella catarrhalis
  • Moraxella lacunata
  • Staphylococcus epidermidis
  • Staphylococcus hominis
  • Staphylococcus lugdunensis
  • Staphylococcus warneri
  • Streptococcus mitis
  • Streptococcus oralis
  • Streptococcus salivarius
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9882
Blood Brain Barrier-0.9103
Caco-2 permeable-0.5689
P-glycoprotein substrateSubstrate0.8063
P-glycoprotein inhibitor INon-inhibitor0.8968
P-glycoprotein inhibitor IINon-inhibitor0.9584
Renal organic cation transporterNon-inhibitor0.7016
CYP450 2C9 substrateNon-substrate0.869
CYP450 2D6 substrateNon-substrate0.8319
CYP450 3A4 substrateNon-substrate0.6463
CYP450 1A2 substrateNon-inhibitor0.7511
CYP450 2C9 inhibitorNon-inhibitor0.8486
CYP450 2D6 inhibitorNon-inhibitor0.8295
CYP450 2C19 inhibitorNon-inhibitor0.7648
CYP450 3A4 inhibitorNon-inhibitor0.6834
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8053
Ames testAMES toxic0.742
CarcinogenicityNon-carcinogens0.8853
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3263 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9278
hERG inhibition (predictor II)Non-inhibitor0.6497
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Suspensionophthalmic0.6 %
Suspensionophthalmic6 mg/mL
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5,447,926 No1995-09-052012-09-05Us
US5447926 No1996-04-132016-04-13Us
US6,685,958 No2004-02-032021-06-20Us
US6,699,492 No2004-03-022019-03-31Us
US6685958 No2001-06-292021-06-29Us
US6699492 No1999-03-312019-03-31Us
US8415342 No2010-11-072030-11-07Us
US8481526 No2011-01-092031-01-09Us
US8604020 No2010-03-122030-03-12Us
US8937062 No2009-11-132029-11-13Us
Properties
StateLiquid
Experimental Properties
PropertyValueSource
water solubilityNot soluble in water MSDS
pKa6.0-7.0MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.143 mg/mLALOGPS
logP0.7ALOGPS
logP0.54ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)5.64ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area86.87 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity101.75 m3·mol-1ChemAxon
Polarizability39 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. O'Brien TP: Besifloxacin ophthalmic suspension, 0.6%: a novel topical fluoroquinolone for bacterial conjunctivitis. Adv Ther. 2012 Jun;29(6):473-90. doi: 10.1007/s12325-012-0027-7. Epub 2012 Jun 20. [PubMed:22729919 ]
  2. Proksch JW, Granvil CP, Siou-Mermet R, Comstock TL, Paterno MR, Ward KW: Ocular pharmacokinetics of besifloxacin following topical administration to rabbits, monkeys, and humans. J Ocul Pharmacol Ther. 2009 Aug;25(4):335-44. doi: 10.1089/jop.2008.0116. [PubMed:19492955 ]
External Links
ATC CodesS01AE08
AHFS Codes
  • 52:04.04
PDB EntriesNot Available
FDA labelDownload (148 KB)
MSDSDownload (159 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
yes
Actions
antagonist
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.
Gene Name:
parC
Uniprot ID:
P43702
Molecular Weight:
83366.24 Da
References
  1. Carter NJ, Scott LJ: Besifloxacin ophthalmic suspension 0.6%. Drugs. 2010;70(1):83-97. doi: 10.2165/11203820-000000000-00000. [PubMed:20030427 ]
Kind
Protein
Organism
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Pharmacological action
yes
Actions
antagonist
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.
Gene Name:
parC
Uniprot ID:
P72525
Molecular Weight:
93132.2 Da
References
  1. Carter NJ, Scott LJ: Besifloxacin ophthalmic suspension 0.6%. Drugs. 2010;70(1):83-97. doi: 10.2165/11203820-000000000-00000. [PubMed:20030427 ]
Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
yes
Actions
antagonist
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.
Gene Name:
gyrA
Uniprot ID:
P43700
Molecular Weight:
97817.145 Da
References
  1. Carter NJ, Scott LJ: Besifloxacin ophthalmic suspension 0.6%. Drugs. 2010;70(1):83-97. doi: 10.2165/11203820-000000000-00000. [PubMed:20030427 ]
Kind
Protein
Organism
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Pharmacological action
yes
Actions
antagonist
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.
Gene Name:
gyrA
Uniprot ID:
P72524
Molecular Weight:
92052.595 Da
References
  1. Carter NJ, Scott LJ: Besifloxacin ophthalmic suspension 0.6%. Drugs. 2010;70(1):83-97. doi: 10.2165/11203820-000000000-00000. [PubMed:20030427 ]
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Drug created on September 14, 2010 10:21 / Updated on June 27, 2016 01:53