TOSUFLOXACIN TOSYLATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H15F3N4O3.C7H8O3S
Molecular Weight	576.544
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=C(C=C1)S(O)(=O)=O.NC2CCN(C2)C3=NC4=C(C=C3F)C(=O)C(=CN4C5=CC=C(F)C=C5F)C(O)=O

InChI

InChIKey=CSSQVOKOWWIUCX-UHFFFAOYSA-N

InChI=1S/C19H15F3N4O3.C7H8O3S/c20-9-1-2-15(13(21)5-9)26-8-12(19(28)29)16(27)11-6-14(22)18(24-17(11)26)25-4-3-10(23)7-25;1-6-2-4-7(5-3-6)11(8,9)10/h1-2,5-6,8,10H,3-4,7,23H2,(H,28,29);2-5H,1H3,(H,8,9,10)

HIDE SMILES / InChI

Description
Sources: http://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966
Curator's Comment: description was created based on several sources, including: http://medical.taishotoyama.co.jp/data/if/pdf/ozx.pdf

Tosufloxacin is a fluoroquinolone antibacterial agent. Tosufloxacin is an inhibitor of bacterial DNA gyrase and topoisomerase IV. Tosufloxacin is indicated for the treatment of various infections such as skin, respiratory, urinary, gynecologic, ophthalmologic, otolaryngologic, dental infections. Fluoroquinolones including tosufloxacin have a potential risk of inducing cartilage and joint toxicity in children. It is also associated with severe thrombocytopenia and nephritis, and hepatotoxicity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial DNA gyrase 66 Target ID: CHEMBL2311224 Sources: http://medical.taishotoyama.co.jp/data/if/pdf/ozx.pdf	Inhibitor 8504
Topoisomerase IV 62 Target ID: CHEMBL2363076 Sources: http://medical.taishotoyama.co.jp/data/if/pdf/ozx.pdf	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Infectious enteritis 5 Sources: http://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	Curative	Approved 8583	Ozex Approved Use It is usually used to treat various infections such as skin/respiratory/urinary/gynecologic/ophthalmologic/otolaryngologic/dental infections. Launch Date 1990
Cystitis 27 Sources: http://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	Curative	Approved 8583	Ozex Approved Use It is usually used to treat various infections such as skin/respiratory/urinary/gynecologic/ophthalmologic/otolaryngologic/dental infections. Launch Date 1990
Prostatitis 25 Sources: http://medical.taishotoyama.co.jp/data/if/pdf/ozx.pdf	Curative	Approved 8583	Ozex Approved Use It is usually used to treat various infections such as skin/respiratory/urinary/gynecologic/ophthalmologic/otolaryngologic/dental infections. Launch Date 1991
Pneumonia 91 Sources: http://medical.taishotoyama.co.jp/data/if/pdf/ozx.pdf	Curative	Approved 8583	Ozex Approved Use It is usually used to treat various infections such as skin/respiratory/urinary/gynecologic/ophthalmologic/otolaryngologic/dental infections. Launch Date 1990

C_max

Value	Dose	Analyte	Population
0.45 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.6 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.83 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.62 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.73 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.82 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
4.09 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TOSUFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
3.84 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TOSUFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
4.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
3.59 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
3.85 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
9.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
10.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11957114/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	TOSUFLOXACIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Food Status: UNKNOWN Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	Disc. AE: Anaphylactoid shock, Toxic epidermal necrolysis... AEs leading to discontinuation/dose reduction: Anaphylactoid shock Toxic epidermal necrolysis Oculomucocutaneous syndrome Convulsion Consciousness abnormal Acute renal failure Interstitial nephritis Liver disorder Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966
300 mg 2 times / day multiple, oral Recommended Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18462354/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/18462354/	Sources: https://pubmed.ncbi.nlm.nih.gov/18462354/

AEs

AE	Significance	Dose	Population
Acute renal failure	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Food Status: UNKNOWN Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966
Anaphylactoid shock	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Food Status: UNKNOWN Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966
Consciousness abnormal	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Food Status: UNKNOWN Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966
Convulsion	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Food Status: UNKNOWN Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966
Interstitial nephritis	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Food Status: UNKNOWN Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966
Liver disorder	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Food Status: UNKNOWN Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966
Oculomucocutaneous syndrome	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Food Status: UNKNOWN Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966
Toxic epidermal necrolysis	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Food Status: UNKNOWN Sources: https://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=33966

PubMed

Title	Date	PubMed
[Intractable pediatric infectious disease: examining the ability of a new drug, tosufloxacin tosilate hydrate for pediatric].	2010-12	21425593
Legionella pneumophila induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages.	2010-11-22	21092200
Cytotoxicity of five fluoroquinolone and two nonsteroidal anti-inflammatory benzalkonium chloride-free ophthalmic solutions in four corneoconjunctival cell lines.	2010-09-20	20922036
[Epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture].	2010-06	20976879
Risk factors for acute prostatitis after transrectal biopsy of the prostate.	2010-06	20577611
[Antibiotic susceptibility of blood-borne Streptococcus pneumoniae and efficacy assessment of respiratory quinolones using Monte Carlo simulation].	2010-02	20836402
Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles.	2009-12-02	19956587
[Efficacy of tosufloxacin in genital chlamydial infections].	2009-10	20055118
Antituberculosis activity of the molecular libraries screening center network library.	2009-09	19783214
Measurement of AQCmax of five different ophthalmic solutions and discussion of its new application.	2009-08	19650709
Levofloxacin 0.5% ophthalmic solution: a review of its use in the treatment of external ocular infections and in intraocular surgery.	2009-06-18	19537841
[Antibacterial activity of quinolones against various clinically isolated strains and evaluation of efficacy based on the pharmacokinetics/pharmacodynamics theory].	2009-06	19882980
Fluoroquinolones reduce carrageenan-induced edema in rats and the involvement of the glucocorticoid receptor system.	2009-04	19396522
Functional characterization of multidrug and toxin extrusion protein 1 as a facilitative transporter for fluoroquinolones.	2009-02	19004926
Corneal deposits after topical tosufloxacin in a patient with poor tear secretion.	2009-01	19092422
Quantitative comparison of the convulsive activity of combinations of twelve fluoroquinolones with five nonsteroidal antiinflammatory agents.	2009	19430173
[Sensitivity surveillance of Haemophilus influenzae isolates for several antibiotics in Gifu Prefecture (2006)].	2008-08	19024643
Antibiotic prophylaxis for transrectal prostate biopsy: a prospective randomized study of tosufloxacin versus levofloxacin.	2008-07	18462354
Mutations in the quinolone resistance determining region in Staphylococcus epidermidis recovered from conjunctiva and their association with susceptibility to various fluoroquinolones.	2008-06	18460536
In vitro susceptibilities of bacterial isolates from conjunctival flora to gatifloxacin, levofloxacin, tosufloxacin, and moxifloxacin.	2008-03	18327047
Multidrug-resistant typhoid fever outbreak in travelers returning from Bangladesh.	2007-12	18258058
[A case of acute bronchitis caused by Neisseria meningitidis associated with HIV infection].	2007-11	18095474
Effect of GrlA mutation on the development of quinolone resistance in Staphylococcus aureus in an in vitro pharmacokinetic model.	2007-11	17827137
[Effectiveness of switch therapy for peritonitis].	2007-08	18018417
A novel in vivo rabbit model that mimics human dosing to determine the distribution of antibiotics in ocular tissues.	2007-08	17803431
Tosufloxacin tosilate-induced thrombocytopenic purpura.	2007-07	17584324
[Antibacterial activity of tosufloxacin against major organisms detected from patients with respiratory infections].	2007-04	17612257
[Susceptibility of clinical isolates from primary care clinics to oral antibacterial agents].	2007-02	17436860
[Evaluation of efficacy of oral quinolone against Streptococcus pneumoniae AND Haemophilus influenzae with the use of Monte Carlo simulation].	2006-12	17334064
[Successful treatment with voriconazole for disseminated cutaneous and visceral infection by Fusarium solani in a patient with acute myeloid leukemia].	2006-08	16986714
Azithromycin failure in Mycoplasma genitalium urethritis.	2006-07	16836839
[Sensitivity surveillance of Streptococcus pneumoniae isolates for several antibiotics in Gifu prefecture (2004)].	2006-06	16913401
Antibacterial activity of tosufloxacin against major organisms detected from patients with respiratory or otorhinological infections: comparison with the results obtained from organisms isolated about 10 years ago.	2006-06	16826349
Pharmacodynamic evaluation of tosufloxacin against Streptococcus pneumoniae in an in vitro model simulating serum concentration.	2006-02	16506083
In vitro activity of sitafloxacin compared with several fluoroquinolones against Streptococcus anginosus and Streptococcus constellatus.	2006-02	16417990
In vitro activity of pazufloxacin, tosufloxacin and other quinolones against Legionella species.	2005-12	16260445
In vitro activity of fluoroquinolones against Mycoplasma genitalium and their bacteriological efficacy for treatment of M. genitalium-positive nongonococcal urethritis in men.	2005-11-01	16206116
[Clinical experience of streptococcal balanoposthitis in 47 healthy adult males].	2005-11	16363705
Antimicrobial activities of tosufloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella branhamella catarrhalis isolated from otolaryngological infectious diseases.	2005-10	16258823
Antimicrobial safety: focus on fluoroquinolones.	2005-07-15	15942881
Prevalence of Ile-460-Val/ParE substitution in clinical Streptococcus pneumoniae isolates that were less susceptible to fluoroquinolones.	2005-07	15942701
Terbium sensitized determination of tosufloxacin using electrochemiluminescence method.	2005-04	15844328
Therapeutic effect of the quinolone prodrug prulifloxacin against experimental urinary tract infections in mice.	1996-12	9006794
N-1-tert-butyl-substituted quinolones: in vitro anti-Mycobacterium avium activities and structure-activity relationship studies.	1996-11	8913479
Structure-activity relationships of quinolone agents against mycobacteria: effect of structural modifications at the 8 position.	1996-10	8891145
[In vitro anti-MAC activities of new quinolones in focus (2)].	1996-09	8999137
Trovafloxacin is active against Toxoplasma gondii.	1996-08	8843293
In-vitro activity of quinolones and macrolides against mycobacteria.	1994-09	7829409
Comparative in-vitro activities of the new quinolone, Bay y 3118, and ciprofloxacin, sparfloxacin, tosufloxacin, CI-960 and CI-990.	1993-04	7605398
Fluoronaphthyridines as antibacterial agents. 4. Synthesis and structure-activity relationships of 5-substituted-6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8- naphthyridine-3-carboxylic acids.	1992-02-07	1738144

Patents

Sample Use Guides

In Vivo Use Guide

In general, for adults, take 2 to 3 tablets (300 to 450 mg of the active ingredient) a day, in 2 to 3 divided doses. The dosage may be adjusted according to disease, symptoms, etc. of the patient. If symptoms are severe or the effect is insufficient, take 4 tablets (600 mg) a day. Osteomyelitis, arthritis: In general, for adults, take 1 tablet (150 mg of the active ingredient) at a time, 3 times a day. The dosage may be adjusted according to disease, symptoms, etc. of the patient. If symptoms are severe or the effect is insufficient, take 4 tablets (600 mg) a day. Typhoid/paratyphoid fever: In general, for adults, take 1 tablet (150 mg of the active ingredient) at a time, 4 times a day for 14 days.

Route of Administration: Oral

In Vitro Use Guide

The MIC90s of tosufloxacin among the 27 isolates of macrolide-resistant Mycoplasma pneumoniae (MRMP) was 0.25 ug/ml and those among the 23 isolates of macrolide-sensitive Mycoplasma pneumoniae (MSMP) was 0.5 μg/ml.

Name

Type

Language

TOSUFLOXACIN TOSILATE

Preferred Name

English

TOSUFLOXACIN TOSYLATE

Common Name

English

Tosufloxacin tosilate [WHO-DD]

Common Name

English

TOSUFLOXACIN TOLUENESULFONATE, (±)-

Common Name

English

TOSUFLOXACIN TOSILATE [MART.]

Common Name

English

TOSUFLOXACIN TOSILATE [JAN]

Common Name

English

1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID, 7-(3-AMINO-1-PYRROLIDINYL)-1-(2,4-DIFLUOROPHENYL)-6-FLUORO-1,4-DIHYDRO-4-OXO-, 4-METHYLBENZENESULFONATE

Common Name

English

TOSUFLOXACIN TOLUENESULFONATE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C795