PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
sparfloxacin

2D structure

Overview

IUPAC Name: 5-amino-1-cyclopropyl-7-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-6,8-difluoro-4-oxoquinoline-3-carboxylic acid
Trade Names: Zagam
PharmGKB Accession Id: PA451472

Description

Sparfloxacin is a fluoroquinolone antibiotic used in the treatment of 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.

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).

ATC Therapeutic Category

  • J01MA:Fluoroquinolones

Pharmacology and Interactions

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.

Pharmacology

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.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Metabolized primarily by phase II glucuronidation to form a glucuronide conjugate. Metabolism does not utilize or interfere with the cytochrome P450 enzyme system.

Protein Binding

Low plasma protein binding in serum at about 45%.

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%.

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).

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.

Chemical Properties

Chemical Formula:

C19H22F2N4O3

SMILES Code:

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

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

392.3998 / 392.166

Curated Information

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
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Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC8
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No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC9
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No phenotype data Genotype Data Available Literature annotations available Not annotated
ADRA1D
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No phenotype data Genotype Data Available Literature annotations available Not annotated
ADRA2A
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Phenotype data available Genotype Data Available Literature annotations available Has annotations
ADRB1
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ADRB2
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
ANK2
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Pathways
Phenotype data available No genotype data Literature annotations available Not annotated
ATP1A1
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
ATP2A1
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
ATP2A2
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
CACNA1C
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
CACNA1D
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
CACNA1G
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
CACNA1H
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Pathways
No phenotype data No genotype data No literature annotations Not annotated
CACNB2
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
CASQ1
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
CASQ2
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No phenotype data Genotype Data Available Literature annotations available Not annotated
CHRM2
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
DSP
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
FKBP1B
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
GJA1
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
GJA5
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
GJD3
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
HCN2
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
HCN4
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Pathways
Phenotype data available No genotype data Literature annotations available Not annotated
JUP
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNA5
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNAB2
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
KCND3
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNE1
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Pathways
No phenotype data Genotype Data Available No literature annotations Not annotated
KCNE1L
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNE2
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
KCNE3
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
KCNE4
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Has annotations
KCNH2
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Publications, Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNIP2
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Pathways
No phenotype data Genotype Data Available Literature annotations available Has annotations
KCNJ11
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ2
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ3
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ4
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ5
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
KCNJ8
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No phenotype data No genotype data Literature annotations available Not annotated
KCNK1
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No phenotype data No genotype data Literature annotations available Not annotated
KCNK3
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Phenotype data available Genotype Data Available Literature annotations available Not annotated
KCNQ1
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No phenotype data No genotype data Literature annotations available Not annotated
LMNA
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
PLN
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
RYR2
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
SCN1B
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Pathways
No phenotype data Genotype Data Available Literature annotations available Not annotated
SCN2B
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No phenotype data Genotype Data Available Literature annotations available Not annotated
SCN3B
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
SCN4B
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Pathways
Phenotype data available Genotype Data Available Literature annotations available Has annotations
SCN5A
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Pathways
No phenotype data No genotype data Literature annotations available Not annotated
SLC8A2
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Pathways
No phenotype data No genotype data No literature annotations Not annotated
SLC8A3
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Pathways

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

PharmGKB Curated Pathways

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Physicochemical determinants of human renal clearance

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01208
ChEBI ID:
9212
KEGG Compound ID:
C07662
KEGG Drug ID:
D00590
PubChem Compound ID:
60464
PubChem Substance ID:
9864

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
The PharmGKB is financially supported by the NIH/ NIGMS and is managed at Stanford University (U01GM61374).
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