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
- 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*
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Bacterial conjunctivitis •••••••••••• •••••••••• - Contraindications & Blackbox Warnings
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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.
Target Actions Organism ADNA topoisomerase 4 subunit A antagonistHaemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) ADNA topoisomerase 4 subunit A antagonistStreptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) ADNA gyrase subunit A antagonistHaemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) ADNA gyrase subunit A antagonistStreptococcus 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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Besifloxacin is combined with Ambroxol. Amisulpride The risk or severity of QTc prolongation can be increased when Besifloxacin is combined with Amisulpride. Articaine The risk or severity of methemoglobinemia can be increased when Besifloxacin is combined with Articaine. Bedaquiline The risk or severity of QTc prolongation can be increased when Besifloxacin is combined with Bedaquiline. Benzocaine The risk or severity of methemoglobinemia can be increased when Besifloxacin is combined with Benzocaine. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Besifloxacin hydrochloride 7506A6J57T 405165-61-9 PMQBICKXAAKXAY-HNCPQSOCSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Besivance Suspension 6 mg/1mL Ophthalmic Bausch & Lomb Incorporated 2009-05-28 Not applicable US Besivance Suspension 0.6 % w/v Ophthalmic Bausch & Lomb Inc 2010-01-27 Not applicable Canada Besivance Suspension 6 mg/1mL Ophthalmic Physicians Total Care, Inc. 2011-07-13 Not applicable US Besivance Suspension 6 mg/1mL Ophthalmic A-S Medication Solutions 2009-05-28 Not applicable US
Categories
- ATC Codes
- S01AE08 — Besifloxacin
- Drug Categories
- Anti-Bacterial Agents
- Anti-Infective Agents
- Antineoplastic Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Enzyme Inhibitors
- Fluoroquinolones
- Heterocyclic Compounds, Fused-Ring
- Moderate Risk QTc-Prolonging Agents
- Ophthalmologicals
- QTc Prolonging Agents
- Quinolines
- Quinolone Antimicrobial
- Quinolones
- Sensory Organs
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- 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
- 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]
- 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]
- FDA Approved Drug Products: Besivance (besifloxacin) ophthalmic suspension [Link]
- External Links
- KEGG Drug
- D08872
- PubChem Compound
- 10178705
- PubChem Substance
- 175427091
- ChemSpider
- 8354210
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Not Available Cataract Surgery / Corneal Health 1 4 Completed Other Cataract Surgery 1 4 Completed Prevention Cataracts 1 4 Completed Treatment Blepharitis 1 4 Completed Treatment Cataracts 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Suspension Ophthalmic 0.6 % w/v Suspension Ophthalmic 6 mg/1mL Suspension Ophthalmic 6.630 mg Suspension Ophthalmic 6 mg/ml Liquid Ophthalmic 6 mg/1ml Suspension Ophthalmic 0.6 % - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6685958 No 2004-02-03 2021-06-20 US US6699492 No 2004-03-02 2019-03-31 US US5447926 No 1995-09-05 2012-09-05 US US8415342 No 2013-04-09 2030-11-07 US US8937062 No 2015-01-20 2029-11-13 US US8481526 No 2013-07-09 2031-01-09 US US8604020 No 2013-12-10 2030-03-12 US
Properties
- State
- Liquid
- Experimental Properties
Property Value Source water solubility Not soluble in water MSDS pKa 6.0-7.0 MSDS - Predicted Properties
Property Value Source Water Solubility 0.143 mg/mL ALOGPS logP 0.7 ALOGPS logP 0.54 Chemaxon logS -3.4 ALOGPS pKa (Strongest Acidic) 5.45 Chemaxon pKa (Strongest Basic) 9.84 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 86.87 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 101.75 m3·mol-1 Chemaxon Polarizability 39.02 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9882 Blood Brain Barrier - 0.9103 Caco-2 permeable - 0.5689 P-glycoprotein substrate Substrate 0.8063 P-glycoprotein inhibitor I Non-inhibitor 0.8968 P-glycoprotein inhibitor II Non-inhibitor 0.9584 Renal organic cation transporter Non-inhibitor 0.7016 CYP450 2C9 substrate Non-substrate 0.869 CYP450 2D6 substrate Non-substrate 0.8319 CYP450 3A4 substrate Non-substrate 0.6463 CYP450 1A2 substrate Non-inhibitor 0.7511 CYP450 2C9 inhibitor Non-inhibitor 0.8486 CYP450 2D6 inhibitor Non-inhibitor 0.8295 CYP450 2C19 inhibitor Non-inhibitor 0.7648 CYP450 3A4 inhibitor Non-inhibitor 0.6834 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8053 Ames test AMES toxic 0.742 Carcinogenicity Non-carcinogens 0.8853 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.3263 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9278 hERG inhibition (predictor II) Non-inhibitor 0.6497
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-002f-0009000000-b3c73c2a9215386d0623 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-009y-0009000000-fc19b14a9a84656e0a78 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-ea06f988bb05e2837837 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000y-0009000000-4871cf86397c606bcd1a Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0l9c-0009000000-30eb19c71b750d94f7e8 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-053s-2009000000-024a2901748749f6282c Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 190.79198 predictedDeepCCS 1.0 (2019) [M+H]+ 193.15 predictedDeepCCS 1.0 (2019) [M+Na]+ 199.75218 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- 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
- 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
- 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
- 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
- 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
- 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]
- 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 at September 14, 2010 16:21 / Updated at February 20, 2024 23:55