Identification
- Summary
Sparfloxacin is a fluoroquinolone antibiotic used to treat bacterial respiratory infections and sinusitis.
- Generic Name
- Sparfloxacin
- DrugBank Accession Number
- DB01208
- Background
Sparfloxacin is a fluoroquinolone antibiotic indicated for bacterial infections. Sparfloxacin exerts its antibacterial activity by inhibiting DNA gyrase, a bacterial topoisomerase. DNA gyrase is an essential enzyme which controls DNA topology and assists in DNA replication, repair, deactivation, and transcription.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
Structure for Sparfloxacin (DB01208)
- Weight
- Average: 392.3998
Monoisotopic: 392.165997 - Chemical Formula
- C19H22F2N4O3
- Synonyms
- cis-5-Amino-1-cyclopropyl-7-(3,5-dimethyl-1-piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
- Sparfloxacin
- External IDs
- AT-4140
- CI-978
Pharmacology
- Indication
For the treatment of adults with the following infections caused by susceptible strains microorganisms: community-acquired pneumonia (caused by Chlamydia pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, or Streptococcus pneumoniae) and acute bacterial exacerbations of chronic bronchitis (caused by Chlamydia pneumoniae, Enterobacter cloacae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Staphylococcus aureus, or Streptococcus pneumoniae).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Acute sinusitis •••••••••••• •••••• Treatment of Chronic obstructive airways disease exacerbated •••••••••••• •••••• Treatment of Community acquired pneumonia (cap) •••••••••••• •••••• Treatment of Susceptible infections •••••••••••• •••••••••• ••••••••••• ••••••••• •••••• - Contraindications & Blackbox Warnings
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Sparfloxacin is a synthetic fluoroquinolone broad-spectrum antimicrobial agent in the same class as ofloxacin and norfloxacin. Sparfloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Sparfloxacin exerts its antibacterial activity by inhibiting DNA gyrase, a bacterial topoisomerase. DNA gyrase is an essential enzyme which controls DNA topology and assists in DNA replication, repair, deactivation, and transcription. Quinolones differ in chemical structure and mode of action from (beta)-lactam antibiotics. Quinolones may, therefore, be active against bacteria resistant to (beta)-lactam antibiotics. Although cross-resistance has been observed between sparfloxacin and other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to sparfloxacin. In vitro tests show that the combination of sparfloxacin and rifampin is antagonistic against Staphylococcus aureus.
- Mechanism of action
The bactericidal action of sparfloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.
Target Actions Organism ADNA gyrase subunit A inhibitorHaemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) ADNA topoisomerase 4 subunit A inhibitorHaemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) ADNA topoisomerase 2-alpha inhibitorHumans - Absorption
Well absorbed following oral administration with an absolute oral bioavailability of 92%. Unaffected by administration with milk or food, however concurrent administration of antacids containing magnesium hydroxide and aluminum hydroxide reduces the oral bioavailability of sparfloxacin by as much as 50%.
- Volume of distribution
Not Available
- Protein binding
Low plasma protein binding in serum at about 45%.
- Metabolism
Hepatic. Metabolized primarily by phase II glucuronidation to form a glucuronide conjugate. Metabolism does not utilize or interfere with the cytochrome P450 enzyme system.
- Route of elimination
Not Available
- Half-life
Mean terminal elimination half-life of 20 hours (range 16-30 hours). Prolonged in patients with renal impairment (creatinine clearance <50 mL/min).
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Single doses of sparfloxacin were relatively non-toxic via the oral route of administration in mice, rats, and dogs. No deaths occurred within a 14-day post-treatment observation period at the highest oral doses tested, up to 5000 mg/kg in either rodent species, or up to 600 mg/kg in the dog. Clinical signs observed included inactivity in mice and dogs, diarrhea in both rodent species, and vomiting, salivation, and tremors in dogs.
- 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 softwareAcarbose The therapeutic efficacy of Acarbose can be increased when used in combination with Sparfloxacin. Aceclofenac Aceclofenac may increase the neuroexcitatory activities of Sparfloxacin. Acemetacin Acemetacin may increase the neuroexcitatory activities of Sparfloxacin. Acenocoumarol The therapeutic efficacy of Acenocoumarol can be increased when used in combination with Sparfloxacin. Acetohexamide The therapeutic efficacy of Acetohexamide can be increased when used in combination with Sparfloxacin. - Food Interactions
- Not Available
Products
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- Zagam
Categories
- ATC Codes
- J01MA09 — Sparfloxacin
- Drug Categories
- Anti-Bacterial Agents
- Anti-Infective Agents
- Antibacterials for Systemic Use
- Antiinfectives for Systemic Use
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Drugs for Treatment of Tuberculosis
- Enzyme Inhibitors
- Fluoroquinolones
- Heterocyclic Compounds, Fused-Ring
- Highest Risk QTc-Prolonging Agents
- P-glycoprotein substrates
- QTc Prolonging Agents
- Quinolines
- Quinolones
- 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 / N-arylpiperazines / Aminoquinolines and derivatives / Haloquinolines / Hydroquinolones / Hydroquinolines / Pyridinecarboxylic acids / Dialkylarylamines / Aryl fluorides / Benzenoids show 13 more
- Substituents
- 1,4-diazinane / Amine / Amino acid / Amino acid or derivatives / Aminoquinoline / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid show 30 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- N-arylpiperazine, quinolone antibiotic, fluoroquinolone antibiotic, quinolone, quinolinemonocarboxylic acid (CHEBI:9212)
- Affected organisms
- Enteric bacteria and other eubacteria
Chemical Identifiers
- UNII
- Q90AGA787L
- CAS number
- 110871-86-8
- InChI Key
- DZZWHBIBMUVIIW-DTORHVGOSA-N
- InChI
- InChI=1S/C19H22F2N4O3/c1-8-5-24(6-9(2)23-8)17-13(20)15(22)12-16(14(17)21)25(10-3-4-10)7-11(18(12)26)19(27)28/h7-10,23H,3-6,22H2,1-2H3,(H,27,28)/t8-,9+
- IUPAC Name
- 5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
- SMILES
- C[C@H]1CN(C[C@@H](C)N1)C1=C(F)C(N)=C2C(=O)C(=CN(C3CC3)C2=C1F)C(O)=O
References
- Synthesis Reference
Guillaume Conrath, "Solution of sparfloxacin, its preparation and salt of which it is composed." U.S. Patent US5478829, issued May, 1987.
US5478829- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015339
- KEGG Drug
- D00590
- KEGG Compound
- C07662
- PubChem Compound
- 60464
- PubChem Substance
- 46506453
- ChemSpider
- 54517
- BindingDB
- 50366822
- 18469
- ChEBI
- 9212
- ChEMBL
- CHEMBL850
- ZINC
- ZINC000000538362
- Therapeutic Targets Database
- DAP000161
- PharmGKB
- PA451472
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Sparfloxacin
- FDA label
- Download (13.3 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 0 Terminated Treatment Osteomyelitis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US4795751 No 1989-01-03 2010-02-04 US 
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Practically insoluble Not Available logP 2.5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.113 mg/mL ALOGPS logP -0.07 ALOGPS logP -0.081 Chemaxon logS -3.5 ALOGPS pKa (Strongest Acidic) 5.56 Chemaxon pKa (Strongest Basic) 8.88 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 98.9 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 101.69 m3·mol-1 Chemaxon Polarizability 39.35 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 + 0.9845 Blood Brain Barrier - 0.967 Caco-2 permeable + 0.8866 P-glycoprotein substrate Substrate 0.8118 P-glycoprotein inhibitor I Non-inhibitor 0.9345 P-glycoprotein inhibitor II Non-inhibitor 0.9183 Renal organic cation transporter Non-inhibitor 0.8154 CYP450 2C9 substrate Non-substrate 0.8794 CYP450 2D6 substrate Non-substrate 0.8787 CYP450 3A4 substrate Non-substrate 0.6465 CYP450 1A2 substrate Non-inhibitor 0.82 CYP450 2C9 inhibitor Non-inhibitor 0.84 CYP450 2D6 inhibitor Non-inhibitor 0.89 CYP450 2C19 inhibitor Non-inhibitor 0.8339 CYP450 3A4 inhibitor Non-inhibitor 0.85 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7377 Ames test AMES toxic 0.6341 Carcinogenicity Non-carcinogens 0.8044 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.9265 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.967 hERG inhibition (predictor II) Non-inhibitor 0.7961
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 206.3141612 predictedDarkChem Lite v0.1.0 [M-H]- 198.2993584 predictedDarkChem Lite v0.1.0 [M-H]- 188.56065 predictedDeepCCS 1.0 (2019) [M+H]+ 206.9218612 predictedDarkChem Lite v0.1.0 [M+H]+ 195.6556132 predictedDarkChem Lite v0.1.0 [M+H]+ 190.95622 predictedDeepCCS 1.0 (2019) [M+Na]+ 206.4512612 predictedDarkChem Lite v0.1.0 [M+Na]+ 201.3671297 predictedDarkChem Lite v0.1.0 [M+Na]+ 196.86873 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Schmitz FJ, Hofmann B, Hansen B, Scheuring S, Luckefahr M, Klootwijk M, Verhoef J, Fluit A, Heinz HP, Kohrer K, Jones ME: Relationship between ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039) MICs and mutations in grlA, grlB, gyrA and gyrB in 116 unrelated clinical isolates of Staphylococcus aureus. J Antimicrob Chemother. 1998 Apr;41(4):481-4. [Article]
- Taba H, Kusano N: Sparfloxacin resistance in clinical isolates of Streptococcus pneumoniae: involvement of multiple mutations in gyrA and parC genes. Antimicrob Agents Chemother. 1998 Sep;42(9):2193-6. [Article]
- Fukuda H, Hori S, Hiramatsu K: Antibacterial activity of gatifloxacin (AM-1155, CG5501, BMS-206584), a newly developed fluoroquinolone, against sequentially acquired quinolone-resistant mutants and the norA transformant of Staphylococcus aureus. Antimicrob Agents Chemother. 1998 Aug;42(8):1917-22. [Article]
- Kind
- Protein
- Organism
- Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Galbraith KM, Ng AC, Eggers BJ, Kuchel CR, Eggers CH, Samuels DS: parC mutations in fluoroquinolone-resistant Borrelia burgdorferi. Antimicrob Agents Chemother. 2005 Oct;49(10):4354-7. [Article]
- Oyamada Y, Ito H, Fujimoto K, Asada R, Niga T, Okamoto R, Inoue M, Yamagishi J: Combination of known and unknown mechanisms confers high-level resistance to fluoroquinolones in Enterococcus faecium. J Med Microbiol. 2006 Jun;55(Pt 6):729-36. [Article]
- Pan XS, Yague G, Fisher LM: Quinolone resistance mutations in Streptococcus pneumoniae GyrA and ParC proteins: mechanistic insights into quinolone action from enzymatic analysis, intracellular levels, and phenotypes of wild-type and mutant proteins. Antimicrob Agents Chemother. 2001 Nov;45(11):3140-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Ubiquitin binding
- Specific Function
- Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...
- Gene Name
- TOP2A
- Uniprot ID
- P11388
- Uniprot Name
- DNA topoisomerase 2-alpha
- Molecular Weight
- 174383.88 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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]
- Skidmore L. (2017). Mosby's Nursing Drug Reference (30th ed.). Elsevier. [ISBN:978-0-323-44826-0]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Symporter activity
- Specific Function
- Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
- Gene Name
- SLC22A5
- Uniprot ID
- O76082
- Uniprot Name
- Solute carrier family 22 member 5
- Molecular Weight
- 62751.08 Da
References
- Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Organic anion transmembrane transporter activity
- Specific Function
- Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- Canalicular multispecific organic anion transporter 1
- Molecular Weight
- 174205.64 Da
References
- Sasabe H, Tsuji A, Sugiyama Y: Carrier-mediated mechanism for the biliary excretion of the quinolone antibiotic grepafloxacin and its glucuronide in rats. J Pharmacol Exp Ther. 1998 Mar;284(3):1033-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Naruhashi K, Tamai I, Inoue N, Muraoka H, Sai Y, Suzuki N, Tsuji A: Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein. J Pharm Pharmacol. 2001 May;53(5):699-709. [Article]
- Cormet-Boyaka E, Huneau JF, Mordrelle A, Boyaka PN, Carbon C, Rubinstein E, Tome D: Secretion of sparfloxacin from the human intestinal Caco-2 cell line is altered by P-glycoprotein inhibitors. Antimicrob Agents Chemother. 1998 Oct;42(10):2607-11. [Article]
Drug created at June 13, 2005 13:24 / Updated at June 09, 2021 08:40