Sparfloxacin

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Approved, Investigational, Withdrawn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
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).

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAcute sinusitis••••••••••••••••••
Treatment ofChronic obstructive airways disease exacerbated••••••••••••••••••
Treatment ofCommunity acquired pneumonia (cap)••••••••••••••••••
Treatment ofSusceptible infections•••••••••••••••••••••• ••••••••••• •••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

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.

TargetActionsOrganism
ADNA gyrase subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
ADNA topoisomerase 4 subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
ADNA topoisomerase 2-alpha
inhibitor
Humans
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
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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
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
AcarboseThe therapeutic efficacy of Acarbose can be increased when used in combination with Sparfloxacin.
AceclofenacAceclofenac may increase the neuroexcitatory activities of Sparfloxacin.
AcemetacinAcemetacin may increase the neuroexcitatory activities of Sparfloxacin.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Sparfloxacin.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be increased when used in combination with Sparfloxacin.
Food Interactions
Not Available

Products

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International/Other Brands
Zagam

Categories

ATC Codes
J01MA09 — Sparfloxacin
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 / 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
Human Metabolome Database
HMDB0015339
KEGG Drug
D00590
KEGG Compound
C07662
PubChem Compound
60464
PubChem Substance
46506453
ChemSpider
54517
BindingDB
50366822
RxNav
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
PhaseStatusPurposeConditionsCount
0TerminatedTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US4795751No1989-01-032010-02-04US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleNot Available
logP2.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.113 mg/mLALOGPS
logP-0.07ALOGPS
logP-0.081Chemaxon
logS-3.5ALOGPS
pKa (Strongest Acidic)5.56Chemaxon
pKa (Strongest Basic)8.88Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area98.9 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity101.69 m3·mol-1Chemaxon
Polarizability39.35 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9845
Blood Brain Barrier-0.967
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.8118
P-glycoprotein inhibitor INon-inhibitor0.9345
P-glycoprotein inhibitor IINon-inhibitor0.9183
Renal organic cation transporterNon-inhibitor0.8154
CYP450 2C9 substrateNon-substrate0.8794
CYP450 2D6 substrateNon-substrate0.8787
CYP450 3A4 substrateNon-substrate0.6465
CYP450 1A2 substrateNon-inhibitor0.82
CYP450 2C9 inhibitorNon-inhibitor0.84
CYP450 2D6 inhibitorNon-inhibitor0.89
CYP450 2C19 inhibitorNon-inhibitor0.8339
CYP450 3A4 inhibitorNon-inhibitor0.85
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7377
Ames testAMES toxic0.6341
CarcinogenicityNon-carcinogens0.8044
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9265 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.967
hERG inhibition (predictor II)Non-inhibitor0.7961
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 GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0fb9-1019000000-5b550920c5bbc4b2c955
MS/MS Spectrum - DI-ESI-qTof , NegativeLC-MS/MSsplash10-052b-0009000000-d679c676e007f977b21f
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000j-0922000000-9b26b987caa87b8a13af
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-1269000000-99d4bb9a3315f1f23139
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000j-0922000000-9b26b987caa87b8a13af
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0009000000-234458bd0b703b0e62b0
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004l-0009000000-35f587a87b53e7f5a17b
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-bbefc55b0558a579e5c5
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-002g-0109000000-f570e19ddf24065b9565
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00p3-0009000000-09bcf160f4829541c8c3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-053r-0019000000-cba078129b53e93a85e0
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-206.3141612
predicted
DarkChem Lite v0.1.0
[M-H]-198.2993584
predicted
DarkChem Lite v0.1.0
[M-H]-188.56065
predicted
DeepCCS 1.0 (2019)
[M+H]+206.9218612
predicted
DarkChem Lite v0.1.0
[M+H]+195.6556132
predicted
DarkChem Lite v0.1.0
[M+H]+190.95622
predicted
DeepCCS 1.0 (2019)
[M+Na]+206.4512612
predicted
DarkChem Lite v0.1.0
[M+Na]+201.3671297
predicted
DarkChem Lite v0.1.0
[M+Na]+196.86873
predicted
DeepCCS 1.0 (2019)

Targets

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insights 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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. 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]
  3. 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]
  4. 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]
  5. 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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. 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]
  3. 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]
  4. 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]
  5. 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
  1. 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
  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]
  3. 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
  1. 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
  1. 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
  1. 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]
  2. 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