U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of SPARFLOXACIN

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

Description
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

Curator's Comment:: sparfloxacin enters the brain poorly mainly because of P-glycoprotein activity at the blood-brain barrier

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
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
Curative
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.1 μg/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
18.7 μg × h/mL
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
20 h
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
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
55%
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%
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

Doses

DosePopulationAdverse 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:
unhealthy, 15 - 99 years
n = 1585
Health Status: unhealthy
Condition: infections
Age Group: 15 - 99 years
Sex: M+F
Population Size: 1585
Sources:
Disc. AE: Photosensitivity reaction...
AEs leading to
discontinuation/dose reduction:
Photosensitivity reaction (11 patient)
Sources:
1600 mg single, oral
Highest studied dose
Dose: 1600 mg
Route: oral
Route: single
Dose: 1600 mg
Sources:
healthy, adult
n = 22
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 22
Sources:
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (4 patients)
Vomiting (3 patients)
Headache (1 patient)
Dizziness (4 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
unhealthy, 15 - 99 years
n = 1585
Health Status: unhealthy
Condition: infections
Age Group: 15 - 99 years
Sex: M+F
Population Size: 1585
Sources:
Headache 1 patient
1600 mg single, oral
Highest studied dose
Dose: 1600 mg
Route: oral
Route: single
Dose: 1600 mg
Sources:
healthy, adult
n = 22
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 22
Sources:
Vomiting 3 patients
1600 mg single, oral
Highest studied dose
Dose: 1600 mg
Route: oral
Route: single
Dose: 1600 mg
Sources:
healthy, adult
n = 22
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 22
Sources:
Dizziness 4 patients
1600 mg single, oral
Highest studied dose
Dose: 1600 mg
Route: oral
Route: single
Dose: 1600 mg
Sources:
healthy, adult
n = 22
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 22
Sources:
Nausea 4 patients
1600 mg single, oral
Highest studied dose
Dose: 1600 mg
Route: oral
Route: single
Dose: 1600 mg
Sources:
healthy, adult
n = 22
Health Status: healthy
Age Group: adult
Sex: M+F
Population Size: 22
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Dual inhibitory activity of sitafloxacin (DU-6859a) against DNA gyrase and topoisomerase IV of Streptococcus pneumoniae.
1999 Oct
Activity of moxifloxacin against mycobacteria.
1999 Sep
Possible relationship between phototoxicity and photodegradation of sitafloxacin, a quinolone antibacterial agent, in the auricular skin of albino mice.
2000 Aug
Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones.
2000 May
Proarrhythmic effects of fluoroquinolone antibacterial agents: in vivo effects as physiologic substrate for torsades.
2000 Nov 15
Anti-toxoplasma activities of 24 quinolones and fluoroquinolones in vitro: prediction of activity by molecular topology and virtual computational techniques.
2000 Oct
Prediction of quinolone activity against Mycobacterium avium by molecular topology and virtual computational screening.
2000 Oct
Mutant prevention concentration as a measure of antibiotic potency: studies with clinical isolates of Mycobacterium tuberculosis.
2000 Sep
History of quinolones and their side effects.
2001
Bactericidal assays for fluoroquinolones.
2001
Inhibitory activity of quinolones against DNA gyrase of Mycobacterium tuberculosis.
2001 Apr
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
In vitro method for prediction of the phototoxic potentials of fluoroquinolones.
2001 Dec
Quinolones and false-positive urine screening for opiates by immunoassay technology.
2001 Dec 26
Quinolones alter defense reactions mediated by macrophages.
2001 Feb
In vitro, ex-vivo and in vivo activities of ethambutol and sparfloxacin alone and in combination against mycobacteria.
2001 Jan
Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG.
2001 Jan
Emergence of cephem- and aztreonam-high-resistant Neisseria gonorrhoeae that does not produce beta-lactamase.
2001 Mar
Effect of some fractions of alveolar surfactant (phospholipids and SP-A) on the bactericidal activity of different antimicrobials against some respiratory pathogens.
2001 Mar
Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics.
2001 Mar
Adverse reactions to fluoroquinolones. an overview on mechanistic aspects.
2001 Mar
In vitro activity of gemifloxacin against Streptococcus pneumoniae isolates in Germany.
2001 Mar-Apr
Activity of moxifloxacin and twelve other antimicrobial agents against 216 clinical isolates of Streptococcus pneumoniae.
2001 Mar-Apr
A comparative study of the fluoroquinolone antibacterial agents on the action potential duration in guinea pig ventricular myocardia.
2001 Nov
Increasing resistance of Streptococcus pneumoniae to fluoroquinolones: results of a Hong Kong multicentre study in 2000.
2001 Nov
Endotoxin impairs biliary transport of sparfloxacin and its glucuronide in rats.
2001 Nov 30
[Comparative study of the bacteriostatic and bactericidal activity of levofloxacin against Pasteurella strains isolated from man].
2001 Oct
In vitro susceptibilities of Bartonella and Rickettsia spp. to fluoroquinolone antibiotics as determined by immunofluorescent antibody analysis of infected Vero cell monolayers.
2001 Sep
Is more than one quinolone needed in clinical practice?
2001 Sep
Molecular epidemiology and mutations at gyrA and parC genes of ciprofloxacin-resistant Escherichia coli isolates from a Taiwan medical center.
2001 Spring
Bactericidal activities of commonly used antiseptics against multidrug-resistant mycobacterium tuberculosis.
2002
[Effectiveness of sparfloxacin (sparflo) in the treatment of complicated forms of pyelonephritis and prostatitis].
2002
A critical review of the fluoroquinolones: focus on respiratory infections.
2002
Comparative study on salivary distribution of fluoroquinolones in rats.
2002 Aug
Comparative antibiotic eradication of mycoplasma infections from continuous cell lines.
2002 Feb
Moxifloxacin sensitivity of respiratory pathogens in the United Kingdom.
2002 Feb
Fluoroquinolones and tuberculosis.
2002 Feb
In-vitro activity of moxifloxacin and other fluoroquinolones against Chlamydia species.
2002 Mar
Possible involvement of P-glycoprotein in the biliary excretion of grepafloxacin.
2002 Mar
Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?
2002 Mar 25
In vitro photochemical clastogenicity of quinolone antibacterial agents studied by a chromosomal aberration test with light irradiation.
2002 May 27
Patents

Sample Use Guides

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
INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
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
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
NCI_THESAURUS C795
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
WHO-ATC J01MA09
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
WHO-VATC QJ01MA09
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
Code System Code Type Description
INN
6612
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
CAS
110871-86-8
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
LACTMED
Sparfloxacin
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
ChEMBL
CHEMBL850
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
NCI_THESAURUS
C61950
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
WIKIPEDIA
SPARFLOXACIN
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
EPA CompTox
110871-86-8
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
MESH
C061363
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
DRUG CENTRAL
2466
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
FDA UNII
Q90AGA787L
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
PUBCHEM
60464
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
RXCUI
18469
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY RxNorm
MERCK INDEX
M10132
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY Merck Index
EVMPD
SUB10610MIG
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY
DRUG BANK
DB01208
Created by admin on Fri Jun 25 21:52:55 UTC 2021 , Edited by admin on Fri Jun 25 21:52:55 UTC 2021
PRIMARY