Details
Stereochemistry | RACEMIC |
Molecular Formula | 2C19H22FN3O4.3H2O |
Molecular Weight | 804.834 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O.O.O.COC1=C(N2CCNC(C)C2)C(F)=CC3=C1N(C=C(C(O)=O)C3=O)C4CC4.COC5=C(N6CCNC(C)C6)C(F)=CC7=C5N(C=C(C(O)=O)C7=O)C8CC8
InChI
InChIKey=RMJMZKDEVNTXHE-UHFFFAOYSA-N
InChI=1S/2C19H22FN3O4.3H2O/c2*1-10-8-22(6-5-21-10)16-14(20)7-12-15(18(16)27-2)23(11-3-4-11)9-13(17(12)24)19(25)26;;;/h2*7,9-11,21H,3-6,8H2,1-2H3,(H,25,26);3*1H2
Gatifloxacin is a recently developed antibacterial agent differing from earlier fluoroquinolones by the presence of a methoxy group at the C-8 position. The presence of the methoxy group has conferred improved antibacterial activity against both Gram-positive and Gram-negative organisms, making gatifloxacin a broad-spectrum antimicrobial agent applicable in many clinical settings. Gatifloxacin is sold under the brand Zymar and is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Aerobic Gram-Positive Bacteria: Cornyebacterium propinquum, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mitis, Streptococcus pneumoniae and Aerobic Gram-Negative Bacteria: Haemophilus influenza. The antibacterial action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. In addition, Gatifloxacin inhibits bacterial topoisomerase IV. This enzyme is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division. The mechanism of action of fluoroquinolones including gatifloxacin is different from that of aminoglycoside, macrolide, and tetracycline antibiotics. Therefore, gatifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to gatifloxacin. There is no cross-resistance between gatifloxacin and the aforementioned classes of antibiotics. Cross-resistance has been observed between systemic gatifloxacin and some other fluoroquinolones.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19497321
Curator's Comment: Known to be CNS penetrant in rats. Human data not available
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2363033 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12019093 |
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Target ID: CHEMBL2311225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9925547 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | ZYMAR Approved UseZYMAXID® (gatifloxacin ophthalmic solution) 0.5% solution is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Aerobic Gram-Positive Bacteria: Staphylococcus aureus Staphylococcus epidermidis Streptococcus mitis group* Streptococcus oralis * Streptococcus pneumoniae Aerobic Gram-Negative Bacteria: Haemophilus influenzae *Efficacy for this organism was studied in fewer than 10 infections. ZYMAXID® ophthalmic solution is a topical fluoroquinolone anti-infective indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Haemophilus influenzae, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mitis group* , Streptococcus oralis * , Streptococcus pneumoniae *Efficacy for this organism was studied in fewer than 10 infections. (1) Launch Date2003 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.2 μg/mL |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
4.6 μg/mL |
400 mg 1 times / day steady-state, intravenous dose: 400 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
4.2 μg/mL |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
3.8 μg/mL |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
5.5 μg/mL |
400 mg single, intravenous dose: 400 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
34.4 μg × h/mL |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
35.4 μg × h/mL |
400 mg 1 times / day steady-state, intravenous dose: 400 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
51 μg × h/mL |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
33 μg × h/mL |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
35.1 μg × h/mL |
400 mg single, intravenous dose: 400 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.1 h |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
13.9 h |
400 mg 1 times / day steady-state, intravenous dose: 400 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
7.8 h |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
7.4 h |
400 mg single, intravenous dose: 400 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
80% |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
80% |
400 mg 1 times / day steady-state, intravenous dose: 400 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
80% |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
80% |
400 mg single, intravenous dose: 400 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GATIFLOXACIN serum | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
10 mg/kg 1 times / day steady, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: steady Dose: 10 mg/kg, 1 times / day Sources: |
unhealthy, 6 - 48 months n = 160 Health Status: unhealthy Condition: acute otitis media Age Group: 6 - 48 months Sex: M Population Size: 160 Sources: |
Disc. AE: Vomiting, Diarrhea... AEs leading to discontinuation/dose reduction: Vomiting (15 patients) Sources: Diarrhea (3 patients) Dehydration (2 patients) Maculopapular rash (2 patients) |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Co-administed with:: glyburide(10 mg/day) Sources: |
unhealthy, 79 years n = 1 Health Status: unhealthy Condition: type 2 diabetes mellitus and pneumonia Age Group: 79 years Sex: M Population Size: 1 Sources: |
Disc. AE: Hyperglycemia... AEs leading to discontinuation/dose reduction: Hyperglycemia (1 patient) Sources: |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Co-administed with:: glyburide(5 mg/day) Sources: |
unhealthy, 84 years n = 1 Health Status: unhealthy Condition: type 2 diabetes mellitus and nonproductive cough Age Group: 84 years Sex: F Population Size: 1 Sources: |
Disc. AE: Hyperglycemia... AEs leading to discontinuation/dose reduction: Hyperglycemia (1 patient) Sources: |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Co-administed with:: metoprolol, diltiazem, subcutaneous heparin, ranitidine, vancomycin, piperacillin/tazobactam, and aspirin Sources: |
unhealthy, 86 years n = 1 Health Status: unhealthy Condition: small bowel obstruction and suspected pneumonia Age Group: 86 years Sex: M Population Size: 1 Sources: |
Disc. AE: Hyperglycemia... AEs leading to discontinuation/dose reduction: Hyperglycemia (1 patient) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Vomiting | 15 patients Disc. AE |
10 mg/kg 1 times / day steady, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: steady Dose: 10 mg/kg, 1 times / day Sources: |
unhealthy, 6 - 48 months n = 160 Health Status: unhealthy Condition: acute otitis media Age Group: 6 - 48 months Sex: M Population Size: 160 Sources: |
Dehydration | 2 patients Disc. AE |
10 mg/kg 1 times / day steady, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: steady Dose: 10 mg/kg, 1 times / day Sources: |
unhealthy, 6 - 48 months n = 160 Health Status: unhealthy Condition: acute otitis media Age Group: 6 - 48 months Sex: M Population Size: 160 Sources: |
Maculopapular rash | 2 patients Disc. AE |
10 mg/kg 1 times / day steady, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: steady Dose: 10 mg/kg, 1 times / day Sources: |
unhealthy, 6 - 48 months n = 160 Health Status: unhealthy Condition: acute otitis media Age Group: 6 - 48 months Sex: M Population Size: 160 Sources: |
Diarrhea | 3 patients Disc. AE |
10 mg/kg 1 times / day steady, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: steady Dose: 10 mg/kg, 1 times / day Sources: |
unhealthy, 6 - 48 months n = 160 Health Status: unhealthy Condition: acute otitis media Age Group: 6 - 48 months Sex: M Population Size: 160 Sources: |
Hyperglycemia | 1 patient Disc. AE |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Co-administed with:: glyburide(10 mg/day) Sources: |
unhealthy, 79 years n = 1 Health Status: unhealthy Condition: type 2 diabetes mellitus and pneumonia Age Group: 79 years Sex: M Population Size: 1 Sources: |
Hyperglycemia | 1 patient Disc. AE |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Co-administed with:: glyburide(5 mg/day) Sources: |
unhealthy, 84 years n = 1 Health Status: unhealthy Condition: type 2 diabetes mellitus and nonproductive cough Age Group: 84 years Sex: F Population Size: 1 Sources: |
Hyperglycemia | 1 patient Disc. AE |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Co-administed with:: metoprolol, diltiazem, subcutaneous heparin, ranitidine, vancomycin, piperacillin/tazobactam, and aspirin Sources: |
unhealthy, 86 years n = 1 Health Status: unhealthy Condition: small bowel obstruction and suspected pneumonia Age Group: 86 years Sex: M Population Size: 1 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/19026171/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10984329/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/19026171/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10984329/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10730688/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18381565/ Page: - |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/20573570/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/20573570/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/17274666/ Page: - |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/20573570/ Page: - |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/11125032/ Page: - |
PubMed
Title | Date | PubMed |
---|---|---|
In vitro and in vivo antibacterial activities of AM-1155, a new 6-fluoro-8-methoxy quinolone. | 1992 Oct |
|
The activity of the methylpiperazinyl fluoroquinolone CG 5501: a comparison with other fluoroquinolones. | 1997 Apr |
|
Comparative in vitro antimicrobial activities of the newly synthesized quinolone HSR-903, sitafloxacin (DU-6859a), gatifloxacin (AM-1155), and levofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex. | 1999 Dec |
|
Mutant prevention concentration as a measure of antibiotic potency: studies with clinical isolates of Mycobacterium tuberculosis. | 2000 Sep |
|
In vitro and in vivo activities of gatifloxacin against Mycobacterium tuberculosis. | 2002 Apr |
|
Possible gatifloxacin-induced fulminant hepatic failure. | 2002 Jul-Aug |
|
Gatifloxacin and ethionamide as the foundation for therapy of tuberculosis. | 2003 Aug |
|
Mycobacterium tuberculosis DNA gyrase: interaction with quinolones and correlation with antimycobacterial drug activity. | 2004 Apr |
|
Short-course treatment regimen to identify potential antituberculous agents in a murine model of tuberculosis. | 2004 Apr |
|
Synthesis of new fluoroquinolones and evaluation of their in vitro activity on Toxoplasma gondii and Plasmodium spp. | 2004 Jun 7 |
|
Torsades de pointes associated with fluoroquinolones: importance of concomitant risk factors. | 2004 Mar |
|
Mutant prevention concentration: comparison of fluoroquinolones and linezolid with Mycobacterium tuberculosis. | 2004 Mar |
|
Action of fluoroquinolones and Linezolid on logarithmic- and stationary-phase culture of Mycobacterium tuberculosis. | 2004 Nov |
|
Rapid microbiologic and pharmacologic evaluation of experimental compounds against Mycobacterium tuberculosis. | 2006 Apr |
|
Design, synthesis and activity against Toxoplasma gondii, Plasmodium spp., and Mycobacterium tuberculosis of new 6-fluoroquinolones. | 2006 Dec |
|
Development and validation of an ion-pairing RP-HPLC method for the estimation of gatifloxacin in bulk and formulations. | 2007 Apr |
|
[Status epilepticus and gatifloxacin]. | 2007 Jan |
|
[A case of multi-drug resistant tuberculosis showing psychiatric adverse effect by cycloserine]. | 2008 Jan |
|
Synthesis and antimycobacterial evaluation of newer 1-cyclopropyl-1,4-dihydro-6-fluoro-7-(substituted secondary amino)-8-methoxy-5-(sub)-4-oxoquinoline-3-carboxylic acids. | 2008 Mar 1 |
|
Antimycobacterial activities of novel fluoroquinolones. | 2009 Jan |
|
In vitro activities of DC-159a, a novel fluoroquinolone, against Mycobacterium species. | 2010 Jun |
|
A comparative analysis of chromosomal aberrations in cultured human lymphocytes due to fluoroquinolone drugs at different expression periods. | 2010 May |
Patents
Sample Use Guides
The recommended dosage regimen for the treatment of bacterial conjunctivitis is: Days 1 and 2: Instill one drop every two hours in the affected eye(s) while awake, up to 8 times daily. Days 3 through 7: Instill one drop up to four times daily while awake.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12697632
Gatifloxacin was synergic with the beta-lactams piperacillin, cefepime and meropenem, and with gentamicin against some drug-resistant pathogens. It was investigated in vitro interaction of gatifloxacin in combination with these drugs against clinical isolates of Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae, vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Synergy was demonstrated with the following combinations at achievable serum concentrations: gatifloxacin/piperacillin for 80% and gatifloxacin/cefepime for 60% of S. maltophilia; gatifloxacin/gentamicin for 60%, and gatifloxacin/cefepime for 50% of ESBL-producing K. pneumoniae, and in all drug combinations for 50-70% of P. aeruginosa. Indifference was noted for the majority of B. cepacia and VRE isolates. Antagonism at therapeutic serum levels was observed with gatifloxacin/piperacillin against a single isolate of B. Cepacia. MIC50 and MIC90 values represent the concentrations at which 50% and 90% of strains, respectively, were inhibited. The gatifloxacin MICs for S. maltophilia ranged from 0.5 to 4 mg/L, the lowest values of the agents tested. Gatifloxacin at 2 mg/L in combination with cefepime at 8 mg/L, and gatifloxacin at 2 mg/L in combination with piperacillin at 64 mg/L, resulted in at least a 2 log10 decrease in viable colonies, and by definition were synergic.
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Classification Tree | Code System | Code | ||
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WHO-ATC |
J01MA16
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WHO-VATC |
QS01AE06
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WHO-ATC |
S01AE06
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WHO-VATC |
QJ01MA16
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NDF-RT |
N0000175937
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NCI_THESAURUS |
C795
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JJ-61
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SUB26363
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Gatifloxacin
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DB01044
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180200-66-2
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m5679
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CHEMBL31
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160738-57-8
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5280
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ACTIVE MOIETY
SUBSTANCE RECORD