Besifloxacin

Identification

Summary

Besifloxacin is a fluoroquinolone antibiotic agent used for the treatment of bacterial conjunctivitis.

Brand Names
Besivance
Generic Name
Besifloxacin
DrugBank Accession Number
DB06771
Background

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

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 393.84
Monoisotopic: 393.125547465
Chemical Formula
C19H21ClFN3O3
Synonyms
  • Besifloxacin
External IDs
  • ISV-403

Pharmacology

Indication

Treatment 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*

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Besifloxacin 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 action

Besifloxacin 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.

TargetActionsOrganism
ADNA topoisomerase 4 subunit A
antagonist
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
ADNA topoisomerase 4 subunit A
antagonist
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
ADNA gyrase subunit A
antagonist
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
ADNA gyrase subunit A
antagonist
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Absorption

Although 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 binding

None

Metabolism

No appreciable metabolism

Route of elimination

N/A

Half-life

The average elimination half-life of besifloxacin in plasma following multiple dosing was estimated to be 7 hours.

Clearance

N/A

Adverse Effects
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Toxicity

LD50, rat: >2000 mg/kg. The most common adverse reaction reported in 2% of patients treated with besifloxacin was conjunctival redness.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AmisulprideThe risk or severity of QTc prolongation can be increased when Besifloxacin is combined with Amisulpride.
EstetrolThe therapeutic efficacy of Estetrol can be decreased when used in combination with Besifloxacin.
FluoxetineThe risk or severity of QTc prolongation can be increased when Fluoxetine is combined with Besifloxacin.
HaloperidolThe risk or severity of QTc prolongation can be increased when Besifloxacin is combined with Haloperidol.
HydroxyzineThe risk or severity of QTc prolongation can be increased when Besifloxacin is combined with Hydroxyzine.
LefamulinLefamulin may increase the QTc-prolonging activities of Besifloxacin.
MagnesiumMagnesium can cause a decrease in the absorption of Besifloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
PitolisantBesifloxacin may increase the QTc-prolonging activities of Pitolisant.
PonesimodThe risk or severity of bradycardia can be increased when Ponesimod is combined with Besifloxacin.
TrazodoneThe risk or severity of QTc prolongation can be increased when Trazodone is combined with Besifloxacin.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Besifloxacin hydrochloride7506A6J57T405165-61-9PMQBICKXAAKXAY-HNCPQSOCSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BesivanceSuspension0.6 % w/vOphthalmicBausch & Lomb Inc2010-01-27Not applicableCanada flag
BesivanceSuspension6 mg/1mLOphthalmicPhysicians Total Care, Inc.2011-07-13Not applicableUS flag
BesivanceSuspension6 mg/1mLOphthalmicA-S Medication Solutions2009-05-28Not applicableUS flag
BesivanceSuspension6 mg/1mLOphthalmicBausch & Lomb Incorporated2009-05-28Not applicableUS flag

Categories

ATC Codes
S01AE08 — Besifloxacin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Quinoline carboxylic acids
Direct Parent
Quinoline carboxylic acids
Alternative Parents
Fluoroquinolones / Chloroquinolines / Aminoquinolines and derivatives / Hydroquinolones / Hydroquinolines / Pyridinecarboxylic acids / Dialkylarylamines / Azepanes / Aryl chlorides / Benzenoids
show 14 more
Substituents
Amine / Amino acid / Amino acid or derivatives / Aminoquinoline / Aromatic heteropolycyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Azacycle / Azepane
show 30 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
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

Chemical Identifiers

UNII
BFE2NBZ7NX
CAS number
141388-76-3
InChI Key
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

References

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. [Article]
  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. [Article]
KEGG Drug
D08872
PubChem Compound
10178705
PubChem Substance
175427091
ChemSpider
8354210
RxNav
819911
ChEBI
135622
ChEMBL
CHEMBL1201760
ZINC
ZINC000003787097
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Besifloxacin
FDA label
Download (148 KB)
MSDS
Download (159 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableCataract Surgery / Corneal Health1
4CompletedOtherCataract Surgery1
4CompletedPreventionCataracts1
4CompletedTreatmentBacterial blepharitis1
4CompletedTreatmentCataracts1
3CompletedTreatmentAcute Bacterial Conjunctivitis2
3CompletedTreatmentBacterial Conjunctivitis1
3CompletedTreatmentKeratitis; Infectious Disease (Manifestation)1
3TerminatedTreatmentBacterial Conjunctivitis2
2CompletedTreatmentBacterial Conjunctivitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SuspensionOphthalmic0.6 % w/v
SuspensionOphthalmic6 mg/1mL
LiquidOphthalmic6 mg/1ml
SuspensionOphthalmic
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6685958No2004-02-032021-06-20US flag
US6699492No2004-03-022019-03-31US flag
US5447926No1995-09-052012-09-05US flag
US8415342No2013-04-092030-11-07US flag
US8937062No2015-01-202029-11-13US flag
US8481526No2013-07-092031-01-09US flag
US8604020No2013-12-102030-03-12US flag

Properties

State
Liquid
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
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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
Uniprot Name
DNA topoisomerase 4 subunit A
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. [Article]
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
Uniprot Name
DNA topoisomerase 4 subunit A
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. [Article]
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, inc...
Gene Name
gyrA
Uniprot ID
P43700
Uniprot Name
DNA gyrase subunit A
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. [Article]
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, inc...
Gene Name
gyrA
Uniprot ID
P72524
Uniprot Name
DNA gyrase subunit A
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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
This drug is a fluoroquinolone, and these agents are known to inhibit CYP1A2.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Zhang L, Wei MJ, Zhao CY, Qi HM: Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes. Acta Pharmacol Sin. 2008 Dec;29(12):1507-14. doi: 10.1111/j.1745-7254.2008.00908.x. [Article]
  2. Shahzadi A, Javed I, Aslam B, Muhammad F, Asi MR, Ashraf MY, Zia-ur-Rahman: Therapeutic effects of ciprofloxacin on the pharmacokinetics of carbamazepine in healthy adult male volunteers. Pak J Pharm Sci. 2011 Jan;24(1):63-8. [Article]

Drug created on September 14, 2010 16:21 / Updated on July 24, 2021 14:58