SPARFLOXACIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H22F2N4O3
Molecular Weight	392.3998
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H]1CN(C[C@@H](C)N1)C2=C(F)C(N)=C3C(=O)C(=CN(C4CC4)C3=C2F)C(O)=O

InChI

InChIKey=DZZWHBIBMUVIIW-DTORHVGOSA-N

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+

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB01208
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20-677S003_Zagam_Prntlbl.pdf

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. 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. Sparfloxacin is used 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). Sparfloxacin has trade names Spacin in Bangladesh, Zagam and Zagam Respipac. Zagam is no longer available in the United States.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA gyrase subunit A 7 Target ID: CHEMBL4165 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11266418	Inhibitor 8297
Streptococcus pneumoniae 25 Target ID: CHEMBL347 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12820807	Inhibitor 8297
Escherichia coli 82 Target ID: CHEMBL354 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11101907	Inhibitor 8297
Haemophilus influenzae 10 Target ID: CHEMBL355 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11101907	Inhibitor 8297
Moraxella catarrhalis 10 Target ID: CHEMBL614429 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11101907	Inhibitor 8297
Topoisomerase IV 62 Target ID: CHEMBL2363076 Sources: http://www.genome.jp/dbget-bin/www_bget?D00590	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Community-acquired pneumonia 47 Sources: http://www.rxlist.com/zagam-drug/indications-dosage.htm	Curative		Approved 8429	Zagam Approved Use Zagam (sparfloxacin) is indicated for the treatment of adults ( ≥ 18 years of age) with the following infections caused by susceptible strains of the designated microorganisms: Community-acquired pneumonia caused by Chlamydia pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, or Streptococcus pneumoniae 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 Launch Date 1996
Chronic bronchitis 51 Sources: http://www.rxlist.com/zagam-drug/indications-dosage.htm	Curative		Approved 8429	Zagam Approved Use Zagam (sparfloxacin) is indicated for the treatment of adults ( ≥ 18 years of age) with the following infections caused by susceptible strains of the designated microorganisms: Community-acquired pneumonia caused by Chlamydia pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, or Streptococcus pneumoniae 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 Launch Date 1996

C_max

Value	Dose	Co-administered	Analyte	Population
1.1 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		SPARFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
1.3 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		SPARFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
18.7 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		SPARFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
20.6 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		SPARFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
20 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		SPARFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
20 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		SPARFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
55% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		SPARFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
55% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		SPARFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10090432/	unhealthy, 15 - 99 years n = 1585 Health Status: unhealthy Condition: infections Age Group: 15 - 99 years Sex: M+F Population Size: 1585 Sources: https://pubmed.ncbi.nlm.nih.gov/10090432/	Disc. AE: Photosensitivity reaction... AEs leading to discontinuation/dose reduction: Photosensitivity reaction (11 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/10090432/
1600 mg single, oral Highest studied dose Dose: 1600 mg Route: oral Route: single Dose: 1600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/	healthy, adult n = 22 Health Status: healthy Age Group: adult Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/	Other AEs: Nausea, Vomiting... Other AEs: Nausea (4 patients) Vomiting (3 patients) Headache (1 patient) Dizziness (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/

AEs

AE	Significance	Dose	Population
Photosensitivity reaction	11 patient Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10090432/	unhealthy, 15 - 99 years n = 1585 Health Status: unhealthy Condition: infections Age Group: 15 - 99 years Sex: M+F Population Size: 1585 Sources: https://pubmed.ncbi.nlm.nih.gov/10090432/
Headache	1 patient	1600 mg single, oral Highest studied dose Dose: 1600 mg Route: oral Route: single Dose: 1600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/	healthy, adult n = 22 Health Status: healthy Age Group: adult Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/
Vomiting	3 patients	1600 mg single, oral Highest studied dose Dose: 1600 mg Route: oral Route: single Dose: 1600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/	healthy, adult n = 22 Health Status: healthy Age Group: adult Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/
Dizziness	4 patients	1600 mg single, oral Highest studied dose Dose: 1600 mg Route: oral Route: single Dose: 1600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/	healthy, adult n = 22 Health Status: healthy Age Group: adult Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/
Nausea	4 patients	1600 mg single, oral Highest studied dose Dose: 1600 mg Route: oral Route: single Dose: 1600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/	healthy, adult n = 22 Health Status: healthy Age Group: adult Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/10397377/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 270 UGT 192 P-gp 1537	MRP2 111

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
MRP2 475	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/18457386/	yes

Drug as victim

Target	Modality	Activity
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf#page=4 Page: 4.0	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11102735/	yes
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf#page=4 Page: 4.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/23711922/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9212	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9212
ChemicalBook	CB7407291	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7407291
MolPort	MolPort-002-507-759	https://www.molport.com/shop/molecule-link/MolPort-002-507-759
Selleck Chemicals	sparfloxacin	http://www.selleckchem.com/products/sparfloxacin.html
ZINC	ZINC000000538362	http://zinc15.docking.org/substances/ZINC000000538362
eMolecules	499196	https://www.emolecules.com/cgi-bin/more?vid=499196

PubMed

Title	Date	PubMed
Dual inhibitory activity of sitafloxacin (DU-6859a) against DNA gyrase and topoisomerase IV of Streptococcus pneumoniae.	1999 Oct	10588315
Comparative antimicrobial activities of the newly synthesized quinolone WQ-3034, levofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex.	2000 Feb	10639351
Anti-toxoplasma activities of 24 quinolones and fluoroquinolones in vitro: prediction of activity by molecular topology and virtual computational techniques.	2000 Oct	10991859
Prediction of quinolone activity against Mycobacterium avium by molecular topology and virtual computational screening.	2000 Oct	10991858
The role of fluoroquinolones in tuberculosis today.	2001	11217874
[Comparison of in vitro antimicrobial activities of ofloxacin, levofloxacin, ciprofloxacin, and sparfloxacin against various mycobacteria].	2001 Apr	11398326
Effects of continuous or pulsed exposure to rifabutin and sparfloxacin on the intracellular growth of Staphylococcus aureus and Mycobacterium tuberculosis.	2001 Apr	11330364
Inhibitory activity of quinolones against DNA gyrase of Mycobacterium tuberculosis.	2001 Apr	11266418
Biochemical effects of sparfloxacin on cell envelope of mycobacteria.	2001 Aug	11811618
Characterization of sparfloxacin-resistant mutants of Staphylococcus aureus obtained in vitro.	2001 Aug	11516932
[Treatment outcomes of multidrug-resistant tuberculosis--comparison between success and failure cases].	2001 Dec	11806128
Quinolones and false-positive urine screening for opiates by immunoassay technology.	2001 Dec 26	11754677
Quinolones alter defense reactions mediated by macrophages.	2001 Feb	11360919
Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG.	2001 Jan	11125032
The in vivo activity of olamufloxacin (HSR-903) in systemic and urinary tract infections in mice.	2001 Jul	11418525
Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolates from Crete, Greece.	2001 Jun	11397616
Pharmacodynamics of moxifloxacin, levofloxacin and sparfloxacin against Streptococcus pneumoniae.	2001 Jun	11389113
Biochemical mechanism of combined effect of ethambutol and sparfloxacin against Mycobacterium smegmatis.	2001 Mar	11495282
Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics.	2001 Mar	11181910
In vitro activity of gemifloxacin against Streptococcus pneumoniae isolates in Germany.	2001 Mar-Apr	11173811
Activity of moxifloxacin and twelve other antimicrobial agents against 216 clinical isolates of Streptococcus pneumoniae.	2001 Mar-Apr	11173809
Uptake of quinolones by in-vitro human monocyte derived macrophages.	2001 May	11370713
Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein.	2001 May	11370709
Effect of different antibacterial agents and surfactant protein-A (SP-A) on adherence of some respiratory pathogens to bronchial epithelial cells.	2001 May	11337228
Increasing resistance of Streptococcus pneumoniae to fluoroquinolones: results of a Hong Kong multicentre study in 2000.	2001 Nov	11679555
Spectrophotometric determination of sparfloxacin in pharmaceutical formulations using bromothymol blue.	2001 Oct	11489396
Comparison of Neisseria gonorrhoeae isolates from the genital tract and pharynx of two gonorrhea patients.	2001 Sep	11810580
In vitro susceptibilities of Bartonella and Rickettsia spp. to fluoroquinolone antibiotics as determined by immunofluorescent antibody analysis of infected Vero cell monolayers.	2001 Sep	11673033
Comparison of the in vitro activities of BMS-284756 and four fluoroquinolones against Streptococcus pneumoniae.	2001 Sep	11533016
Development and validation of a nonaqueous titration with perchloric acid to determine sparfloxacin in tablets.	2001 Sep	11522490
[Effectiveness of sparfloxacin (sparflo) in the treatment of complicated forms of pyelonephritis and prostatitis].	2002	11898727
A critical review of the fluoroquinolones: focus on respiratory infections.	2002	11790155
[Prospects for development of new antituberculous drugs].	2002 Aug	12235850
Comparative study on salivary distribution of fluoroquinolones in rats.	2002 Aug	12186414
Comparative antibiotic eradication of mycoplasma infections from continuous cell lines.	2002 Feb	11929000
In vitro activity of clinafloxacin in comparison with other quinolones against Stenotrophomonas maltophilia clinical isolates in the presence and absence of reserpine.	2002 Feb	11858908
Elimination of mycoplasma from leukemia-lymphoma cell lines using antibiotics.	2002 Feb	11840296
Fluoroquinolones and tuberculosis.	2002 Feb	11829714
Preparation and characterization of sparfloxacin-beta-cyclodextrin complexes.	2002 Jul	12168542
Electrochemical analysis of sparfloxacin in pharmaceutical formulation and biochemical screening of its Co(II) complex.	2002 Jul 31	12093511
[Drug interactions between nonsteroidal anti-inflammatory drug and pazufloxacin mesilate, a new quinolone antibacterial agent for intravenous use: convulsions in mice after intravenous or intracerebroventricular administration].	2002 Jun	12199111
[Phototoxicity studies of pazufloxacin mesilate, a novel parenteral quinolone antimicrobial agent--in vitro and in vivo studies].	2002 Jun	12199110
Molecular characterization of the genes encoding DNA gyrase and topoisomerase IV of Listeria monocytogenes.	2002 Jun	12039883
[A case report of pulmonary nocardiosis associated with bronchiectasis after pulmonary tuberculosis successfully treated with sparfloxacin].	2002 Mar	11974891
Possible involvement of P-glycoprotein in the biliary excretion of grepafloxacin.	2002 Mar	11906478

Patents

Sample Use Guides

In Vivo Use Guide

The recommended daily dose of Zagam (sparfloxacin) in patients with normal renal function is two 200-mg tablets taken on the first day as a loading dose. Thereafter, one 200-mg tablet should be taken every 24 hours for a total of 10 days of therapy (11 tablets). The recommended daily dose of Zagam (sparfloxacin) in patients with renal impairment (creatinine clearance < 50 mL/min) is two 200-mg tablets taken on the first day as a loading dose. Thereafter, one 200-mg tablet should be taken every 48 hours for a total of 9 days of therapy (6 tablets).

Route of Administration: Oral

In Vitro Use Guide

Sparfloxacin inhibits most anaerobes at < or = 2 ug/mL

Name

Type

Language

SPARFLOXACIN

Official Name

English

SPARFLOXACIN [USAN]

Common Name

English

SPARFLOXACIN [MI]

Common Name

English

NSC-759641

Code

English

SPARFLOXACIN [JAN]

Common Name

English

ZAGAM

Brand Name

English

AT-4140

Code

English

3-QUINOLINECARBOXYLIC ACID, 5-AMINO-1-CYCLOPROPYL-7-(3,5-DIMETHYL-1-PIPERAZINYL)-6,8-DIFLUORO-1,4-DIHYDRO-4-OXO-, CIS-

Systematic Name

English

Sparfloxacin [WHO-DD]

Common Name

English

SPARFLOXACIN [MART.]

Common Name

English

SPARFLOXACIN [VANDF]

Common Name

English

CI-978

Code

English

SPARFLOXACIN [ORANGE BOOK]

Common Name

English

sparfloxacin [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C280