SITAFLOXACIN

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	2C19H18ClF2N3O3.3H2O
Molecular Weight	873.674
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

O.O.O.N[C@@H]1CN(CC12CC2)C3=C(Cl)C4=C(C=C3F)C(=O)C(=CN4[C@@H]5C[C@@H]5F)C(O)=O.N[C@@H]6CN(CC67CC7)C8=C(Cl)C9=C(C=C8F)C(=O)C(=CN9[C@@H]%10C[C@@H]%10F)C(O)=O

InChI

InChIKey=MPORYQCGWFQFLA-ONPDANIMSA-N

InChI=1S/2C19H18ClF2N3O3.3H2O/c2*20-14-15-8(17(26)9(18(27)28)5-25(15)12-4-10(12)21)3-11(22)16(14)24-6-13(23)19(7-24)1-2-19;;;/h2*3,5,10,12-13H,1-2,4,6-7,23H2,(H,27,28);3*1H2/t2*10-,12+,13+;;;/m00.../s1

HIDE SMILES / InChI

Description

Sitafloxacin hydrate (DU-6859a, Gracevit), a new-generation, broad-spectrum oral fluoroquinolone that is very active against many Gram-positive, Gram-negative and anaerobic clinical isolates, including strains resistant to other fluoroquinolones, was recently approved in Japan for the treatment of respiratory and urinary tract infections. This is a new quinolone oral antibacterial to inhibit DNA replication of bacteria at the time of infection, and shows antibacterial action. Sitafloxacin is active against methicillin-resistant staphylococci, Streptococcus pneumoniae and other streptococci with reduced susceptibility to levofloxacin and other quinolones and enterococci. Sitafloxacin has also demonstrated activity against clinical isolates of Klebsiella pneumoniae (including about 67% of strains producing extended-spectrum, beta-lactamases and resistant to ciprofloxacin), Enterobacter cloacae, Pseudomonas aeruginosa with some activity against quinolone-resistant strains and Acinetobacter baumannii. The in vitro activity against anaerobes is comparable to imipenem or metronidazole. Sitafloxacin showed dual inhibitory activity against both enzymes: Streptococcus pneumoniae DNA gyrase and topoisomerase IV.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Topoisomerase IV 62	Inhibitor 8,297
DNA gyrase 26	Inhibitor 8,297

Conditions

Condition	Modality	Highest Phase	Product
Respiratory infections 12	Curative	Approved 8,429	Gracevit(R)
Urologic infection 3	Curative	Approved 8,429	Gracevit(R)
Gynecologic infections 18	Curative	Approved 8,429	Gracevit(R)
Otorhinological infections 5	Curative	Approved 8,429	Gracevit(R)
Dental infection 3	Curative	Approved 8,429	Gracevit(R)

C_max

Value	Dose	Analyte	Population
0.29 μg/mL	25 mg single, oral	SITAFLOXACIN serum	Homo sapiens
0.51 μg/mL	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
1 μg/mL	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
1.86 μg/mL	200 mg single, oral	SITAFLOXACIN serum	Homo sapiens
0.88 μg/mL	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
0.38 μg/mL	50 mg 2 times / day multiple, oral	SITAFLOXACIN serum	Homo sapiens
0.5 μg/mL	50 mg 2 times / day multiple, oral	SITAFLOXACIN serum	Homo sapiens
0.84 μg/mL	100 mg 2 times / day multiple, oral	SITAFLOXACIN serum	Homo sapiens
1.09 μg/mL	100 mg 2 times / day multiple, oral	SITAFLOXACIN serum	Homo sapiens
0.61 μg/mL	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
0.91 μg/mL	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
0.63 μg/mL	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
0.75 μg/mL	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
0.6 μg/mL	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
3.44 μg/mL	400 mg 2 times / day multiple, intravenous	SITAFLOXACIN plasma	Homo sapiens
4.2 μg/mL	400 mg 2 times / day steady-state, intravenous	SITAFLOXACIN plasma	Homo sapiens
5.08 μg/mL	600 mg 2 times / day multiple, intravenous	SITAFLOXACIN plasma	Homo sapiens
6.44 μg/mL	600 mg 2 times / day steady-state, intravenous	SITAFLOXACIN plasma	Homo sapiens
7.18 μg/mL	800 mg 2 times / day multiple, intravenous	SITAFLOXACIN plasma	Homo sapiens
9.07 μg/mL	800 mg 2 times / day steady-state, intravenous	SITAFLOXACIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
1.52 μg × h/mL	25 mg single, oral	SITAFLOXACIN serum	Homo sapiens
2.62 μg × h/mL	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
5.55 μg × h/mL	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
12.04 μg × h/mL	200 mg single, oral	SITAFLOXACIN serum	Homo sapiens
5.81 μg × h/mL	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
2.2 μg × h/mL	50 mg 2 times / day multiple, oral	SITAFLOXACIN serum	Homo sapiens
2.71 μg × h/mL	50 mg 2 times / day multiple, oral	SITAFLOXACIN serum	Homo sapiens
4.34 μg × h/mL	100 mg 2 times / day multiple, oral	SITAFLOXACIN serum	Homo sapiens
5.9 μg × h/mL	100 mg 2 times / day multiple, oral	SITAFLOXACIN serum	Homo sapiens
6.35 μg × h/mL	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
4.86 μg × h/mL	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
4.66 μg × h/mL	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
8.04 μg × h/mL	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
9.95 μg × h/mL	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
17.23 μg × h/mL	400 mg 2 times / day multiple, intravenous	SITAFLOXACIN plasma	Homo sapiens
24.16 μg × h/mL	400 mg 2 times / day steady-state, intravenous	SITAFLOXACIN plasma	Homo sapiens
27.32 μg × h/mL	600 mg 2 times / day multiple, intravenous	SITAFLOXACIN plasma	Homo sapiens
39.12 μg × h/mL	600 mg 2 times / day steady-state, intravenous	SITAFLOXACIN plasma	Homo sapiens
38.09 μg × h/mL	800 mg 2 times / day multiple, intravenous	SITAFLOXACIN plasma	Homo sapiens
56.36 μg × h/mL	800 mg 2 times / day steady-state, intravenous	SITAFLOXACIN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
5.2 h	25 mg single, oral	SITAFLOXACIN serum	Homo sapiens
6.2 h	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
5.7 h	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
5.3 h	200 mg single, oral	SITAFLOXACIN serum	Homo sapiens
5.5 h	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
5.1 h	50 mg 2 times / day multiple, oral	SITAFLOXACIN serum	Homo sapiens
4.6 h	100 mg 2 times / day multiple, oral	SITAFLOXACIN serum	Homo sapiens
6 h	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
3.3 h	100 mg single, oral	SITAFLOXACIN serum	Homo sapiens
7.5 h	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
11.5 h	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens
16.3 h	50 mg single, oral	SITAFLOXACIN serum	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
45%	100 mg single, oral		SITAFLOXACIN serum	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
100 mg 2 times / day multiple, oral Studied dose	unhealthy	Other AEs: Diarrhea, Alanine aminotransferase increase...
400 mg 1 times / day multiple, intravenous Studied dose	unhealthy	Other AEs: fever, Congestive cardiac failure...

Showing 1 to 2 of 2 entries

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AEs

Show entries

AE	Significance	Dose	Population
Fatigue	0.9%	100 mg 2 times / day multiple, oral Studied dose	unhealthy
Platelet count increased	0.9%	100 mg 2 times / day multiple, oral Studied dose	unhealthy
Vomiting	0.9%	100 mg 2 times / day multiple, oral Studied dose	unhealthy
Dizziness	1.8%	100 mg 2 times / day multiple, oral Studied dose	unhealthy
Aspartate aminotransferase increase	2.6%	100 mg 2 times / day multiple, oral Studied dose	unhealthy

Showing 1 to 5 of 13 entries

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PubMed

Show entries

Title	Date	PubMed
In vitro and in vivo antifungal activities of DU-6859a, a fluoroquinolone, in combination with amphotericin B and fluconazole against pathogenic fungi.	1995 Jul	7492096
Inhibitory activity of quinolones against DNA gyrase of Mycobacterium tuberculosis.	2001 Apr	11266418
Recent advances in the field of quinolones.	2001 Jan-Feb	11347964
In vitro activity of sitafloxacin against Clostridium difficile.	2001 May	11328798
A comparative study of the fluoroquinolone antibacterial agents on the action potential duration in guinea pig ventricular myocardia.	2001 Nov	11885973

Showing 1 to 5 of 44 entries

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Patents

Sample Use Guides

In Vivo Use Guide

for adults: 1 tablet (50 mg of sitafloxacin) at a time, twice daily, or 2 tablets (100 mg) at a time, once daily. If the effect is insufficient, the dosage may be increased to 2 tablets (100 mg) at a time, twice daily.

Route of Administration: Oral

In Vitro Use Guide

The minimum inhibitory concentration of sitafloxacin (STFX) at which 90% of isolates (MIC90) was 0.5 microg/mL for methicillin-susceptible Staphylococcus aureus. STFX inhibited the growth of all the isolates of Streptococcus pneumoniae at 0.06 microg/mL or less. The MIC90 of STFX was 0.03 microg/mL. Against Streptococcus pyogenes, the MIC90 of STFX was 0.06 microg/mL. The MIC90 of STFX was 2 microg/mL for Enterococcus faecalis. The MIC90 of STFX for Escherichia coli was 2 microg/mL. The MIC90 of STFX for Pseudomonas aeruginosa isolates recovered from urinary infections was 4 microg/mL. The MIC90 of STFX for P. aeruginosa isolates recovered from respiratory infections was 4 microg/mL. STFX inhibited the growth of all the isolates of Haemophilus influenzae at 0.004 microg/mL or less. The MIC90 of STFX was 0.015 microg/mL for Moraxella catarrhalis. The MIC90(s) of STFX ranged from 0.03 to 0.25 microg/mL for all the species of anaerobic bacteria and were the lowest values of all the antimicrobial agents tested

Show entries

Name

Type

Language

SITAFLOXACIN

Official Name

English

3-QUINOLINECARBOXYLIC ACID, 7-(7-AMINO-5-AZASPIRO(2.4)HEPT-5-YL)-8-CHLORO-6-FLUORO-1-(2-FLUOROCYCLOPROPYL)-1,4-DIHYDRO-4-OXO-, HYDRATE (2:3), (1R-(1.ALPHA.(S*), 2.ALPHA.))-

Common Name

English

SITAFLOXACIN HYDRATE

Common Name

English

DU-6859A

Code

English

SITAFLOXACIN [USAN]

Common Name

English

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Classification Tree

Code System

Code

Fluoroquinolones

WHO-VATC

QJ01MA21

Fluoroquinolones

WHO-ATC

J01MA21

Antibiotic

NCI_THESAURUS

C795

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Code System

Code

Type

Description

FDA UNII

9TD681796G

PRIMARY

WIKIPEDIA

SITAFLOXACIN

PRIMARY

NCI_THESAURUS

C76922

PRIMARY

DRUG BANK

DB13261

PRIMARY

MERCK INDEX

m9959

PRIMARY

Merck Index

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ACTIVE MOIETY


					3GJC60U4Q8

SITAFLOXACIN ANHYDROUS

SUBSTANCE RECORD


					9TD681796G

SITAFLOXACIN

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound