SPARFLOXACIN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H22F2N4O3
Molecular Weight	392.4005
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@]1([H])CN(C[C@@]([H])(C)N1)c2c(c(c3c(c2F)n(cc(c3=O)C(=O)O)C4CC4)N)F

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

Molecular Formula	C19H22F2N4O3
Molecular Weight	392.4005
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 6 Target ID: CHEMBL4165 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11266418	Inhibitor 7728
Streptococcus pneumoniae 20 Target ID: CHEMBL347 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12820807	Inhibitor 7728
Escherichia coli 78 Target ID: CHEMBL354 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11101907	Inhibitor 7728
Haemophilus influenzae 9 Target ID: CHEMBL355 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11101907	Inhibitor 7728
Moraxella catarrhalis 7 Target ID: CHEMBL614429 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11101907	Inhibitor 7728
Topoisomerase IV 56 Target ID: CHEMBL2363076 Sources: http://www.genome.jp/dbget-bin/www_bget?D00590	Inhibitor 7728

Conditions

Condition	Modality	Targets	Highest Phase	Product
Community-acquired pneumonia 39 Sources: http://www.rxlist.com/zagam-drug/indications-dosage.htm	Curative		Approved 8043	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 8.5086719E11
Chronic bronchitis 48 Sources: http://www.rxlist.com/zagam-drug/indications-dosage.htm	Curative		Approved 8043	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 8.5086719E11

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 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 236 UGT 173 P-gp 1400	MRP2 107

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
MRP2 434	inducer 1440 Sources: https://pubmed.ncbi.nlm.nih.gov/18457386/	yes

Drug as victim

Target	Modality	Activity
CYP 236	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf#page=4 Page: 4.0	no
P-gp 1400	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/11102735/	yes
UGT 173	substrate 3113 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 1507	inhibitor 1489 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
Latest industry information on the safety profile of levofloxacin in Japan.	2001	11549788
Evidence of different profiles of side effects and drug-drug interactions among the quinolones--the pharmacokinetic standpoint.	2001	11549786
Biochemical effects of sparfloxacin on cell envelope of mycobacteria.	2001 Aug	11811618
Activity of telithromycin against 26 quinolone-resistant pneumococci with known quinolone-resistance mechanisms.	2001 Dec	11843916
[Treatment outcomes of multidrug-resistant tuberculosis--comparison between success and failure cases].	2001 Dec	11806128
A pharmacokinetic/pharmacodynamic approach to show that not all fluoroquinolones exhibit similar sensitivity toward the proconvulsant effect of biphenyl acetic acid in rats.	2001 Dec	11733465
In vitro method for prediction of the phototoxic potentials of fluoroquinolones.	2001 Dec	11698174
Quinolones and false-positive urine screening for opiates by immunoassay technology.	2001 Dec 26	11754677
[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). III. Secular changes in susceptibility].	2001 Jun	11525192
A comparative study of the fluoroquinolone antibacterial agents on the action potential duration in guinea pig ventricular myocardia.	2001 Nov	11885973
N1-phenyl substituted 4-quinolones of tuberculostatic activity.	2001 Nov	11817167
Increasing resistance of Streptococcus pneumoniae to fluoroquinolones: results of a Hong Kong multicentre study in 2000.	2001 Nov	11679555
Endotoxin impairs biliary transport of sparfloxacin and its glucuronide in rats.	2001 Nov 30	11734193
Fluoroquinolone susceptibilities of efflux-mediated multidrug-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia.	2001 Oct	11581236
Relationship between mutations in the DNA gyrase and topoisomerase IV genes and nadifloxacin resistance in clinically isolated quinolone-resistant Staphylococcus aureus.	2001 Sep	11810583
Comparison of Neisseria gonorrhoeae isolates from the genital tract and pharynx of two gonorrhea patients.	2001 Sep	11810580
[Multidrug-resistant and fluoroquinolone-resistant Salmonella enterica serotype Typhimurium definitive phage type 12 isolated from infantile diarrhea].	2001 Sep	11605192
Is more than one quinolone needed in clinical practice?	2001 Sep	11573860
Development and validation of a nonaqueous titration with perchloric acid to determine sparfloxacin in tablets.	2001 Sep	11522490
In vitro activity of novel fluoroquinolones against Streptococcus pneumoniae isolated from children with acute otitis media.	2001 Sep-Oct	11561138
[Sparfloxacin (a long-acting difluoroquinolone)--an antibacterial preparation with the broad spectrum activity].	2002	12077937
[Sparfloxacin (Sparflo) in the treatment of urological infections].	2002	12077935
Bactericidal activities of commonly used antiseptics against multidrug-resistant mycobacterium tuberculosis.	2002	12011515
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
Pharmacodynamic characterization of efflux and topoisomerase IV-mediated fluoroquinolone resistance in Streptococcus pneumoniae.	2002 Aug	12161401
Comparative antibiotic eradication of mycoplasma infections from continuous cell lines.	2002 Feb	11929000
Minimal inhibitory concentrations and time-kill determination of moxifloxacin against aerobic and anaerobic isolates.	2002 Feb	11850163
Elimination of mycoplasma from leukemia-lymphoma cell lines using antibiotics.	2002 Feb	11840296
Fluoroquinolones and tuberculosis.	2002 Feb	11829714
Clinical toxicological aspects of fluoroquinolones.	2002 Feb 28	12052667
[Efficacy of the sparfloxacin-ethambutol combination in a case of cerebral tuberculosis].	2002 Jan	11859701
Influence of CO(2) incubation on quinolone activity against Streptococcus pneumoniae and Haemophilus influenzae.	2002 Jan	11821174
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
Streptococcus pneumoniae, Brooklyn, New York: fluoroquinolone resistance at our doorstep.	2002 Jun	12023915
[A case report of pulmonary nocardiosis associated with bronchiectasis after pulmonary tuberculosis successfully treated with sparfloxacin].	2002 Mar	11974891
In-vitro activity of moxifloxacin and other fluoroquinolones against Chlamydia species.	2002 Mar	11957133
Possible involvement of P-glycoprotein in the biliary excretion of grepafloxacin.	2002 Mar	11906478
Activity of clinafloxacin, compared with six other quinolones, against Acinetobacter baumannii clinical isolates.	2002 Mar	11864947
In vitro antibacterial activities of DQ-113, a potent quinolone, against clinical isolates.	2002 Mar	11850285
[Use of sparfloxacin (Sparflo) in treating complicated urologic infections].	2002 Mar-Apr	12077817
[Pulmonary infection caused by Mycobacterium szulgai: a case report].	2002 May	12073621
Serial passage of Chlamydia spp. in sub-inhibitory fluoroquinolone concentrations.	2002 May	12003968
A novel approach to determining physicochemical and absorption properties of 6-fluoroquinolone derivatives: experimental assessment.	2002 May	11976020
In vitro photochemical clastogenicity of quinolone antibacterial agents studied by a chromosomal aberration test with light irradiation.	2002 May 27	12034313

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

Substance Class	Chemical Created by `admin` on `Fri Jun 25 21:52:55 UTC 2021` Edited by `admin` on `Fri Jun 25 21:52:55 UTC 2021`
Record UNII	Q90AGA787L
Record Status	`Validated (UNII)`
Record Version

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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