GREPAFLOXACIN

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H22FN3O3
Molecular Weight	359.3947
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1CN(CCN1)C2=C(F)C(C)=C3C(=O)C(=CN(C4CC4)C3=C2)C(O)=O

InChI

InChIKey=AIJTTZAVMXIJGM-UHFFFAOYSA-N

InChI=1S/C19H22FN3O3/c1-10-8-22(6-5-21-10)15-7-14-16(11(2)17(15)20)18(24)13(19(25)26)9-23(14)12-3-4-12/h7,9-10,12,21H,3-6,8H2,1-2H3,(H,25,26)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20-695S003_Raxar_Prntlbl.pdf
Curator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20-695_Raxar_Pharma.pdf | https://www.drugbank.ca/drugs/DB00365

Grepafloxacin is a monofluorinated quinolone with a cyclopropyl group at position 1, a 3-methyl-1piperazinyl group at position 7 and a methyl substitution at the 5 position, that was synthesized by Otsuka in Japan. It exhibited in vitro activity against a wide variety of both Gram-positive and Gram-negative bacteria including anaerobic species. The compound was reported to have a broad spectrum of activity, particularly against pathogens responsible for community-acquired respiratory infections including those caused by beta-lactam and macrolide-resistant strains of Streptococcus pneumoniae and Haemophilus influenzae. Japanese researchers also reported that unlike other quinolones, grepafloxacin reached high levels in the bile and might also be useful in the treatment of biliary tract infection. Grepafloxacin was administered once daily and did not require dosage adjustment for renal insufficiency, but grepafloxacin tablets were contraindicated in patients with hepatic failure. Otsuka Pharmaceutical signed a licensing agreement for grepafloxacin with GlaxoSmithKline. According to this agreement, GlaxoSmithKline had marketing rights to grepafloxacin in Europe, USA, and certain other markets. Otsuka retained rights for Japan and some Asian countries

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Topoisomerase IV 62 Target ID: CHEMBL2363076 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10824040	Inhibitor 8297
DNA topoisomerase II 66 Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10824040	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Acute bacterial exacerbations of chronic bronchitis caused by Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20-695S003_Raxar_Prntlbl.pdf	Curative	Withdrawn	RAXAR Approved Use RAXAR Tablets are Indicated for treatment of adults with mild to moderate infections caused by susceptible strains of the designated microorganisms in the infections listed below: Acute Bacterial Exacerbations of Chronic Bronchitis caused by Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis. Community-acquired Pneumonia caused by Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, or Mycoplasma pneumonia. Uncomplicated Gonorrhea (urethral In males and endocervical and rectal in females) caused by Neissen'a gononrhoeae. Nongonococcal Urethritis and Cervicitis caused by Chlamydia trachomatis Launch Date 1997
Community-acquired pneumonia caused by Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, or Mycoplasma pneumonia 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20-695S003_Raxar_Prntlbl.pdf	Curative	Withdrawn	RAXAR Approved Use RAXAR Tablets are Indicated for treatment of adults with mild to moderate infections caused by susceptible strains of the designated microorganisms in the infections listed below: Acute Bacterial Exacerbations of Chronic Bronchitis caused by Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis. Community-acquired Pneumonia caused by Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, or Mycoplasma pneumonia. Uncomplicated Gonorrhea (urethral In males and endocervical and rectal in females) caused by Neissen'a gononrhoeae. Nongonococcal Urethritis and Cervicitis caused by Chlamydia trachomatis Launch Date 1997
Uncomplicated gonorrhea (urethral In males and endocervical and rectal in females) caused by Neissen'a gononrhoeae 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20-695S003_Raxar_Prntlbl.pdf	Curative	Withdrawn	RAXAR Approved Use RAXAR Tablets are Indicated for treatment of adults with mild to moderate infections caused by susceptible strains of the designated microorganisms in the infections listed below: Acute Bacterial Exacerbations of Chronic Bronchitis caused by Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis. Community-acquired Pneumonia caused by Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, or Mycoplasma pneumonia. Uncomplicated Gonorrhea (urethral In males and endocervical and rectal in females) caused by Neissen'a gononrhoeae. Nongonococcal Urethritis and Cervicitis caused by Chlamydia trachomatis Launch Date 1997

C_max

Value	Dose	Analyte	Population
1.43 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.63 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.93 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.41 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.26 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.17 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.47 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
14.6 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
32.2 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
11.35 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
19.73 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
27.69 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
45.04 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.08 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
11.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
12.67 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
12.25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
11.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
10.14 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Analyte	Population
50% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
50% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
50% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
50% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
50% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
50% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
50% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9433650	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	GREPAFLOXACIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9449270/	unhealthy, 47.7 years n = 207 Health Status: unhealthy Condition: infections Age Group: 47.7 years Sex: M+F Population Size: 207 Sources: https://pubmed.ncbi.nlm.nih.gov/9449270/	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea (3 patients) Vomiting (1 patient) Taste perversion (2 patients) Dizziness (3 patients) Diarrhea (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/9449270/
600 mg 1 times / day steady, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9449270/	unhealthy, 48.4 years n = 204 Health Status: unhealthy Condition: infections Age Group: 48.4 years Sex: M+F Population Size: 204 Sources: https://pubmed.ncbi.nlm.nih.gov/9449270/	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea (8 patients) Vomiting (4 patients) Taste perversion (5 patients) Dizziness (3 patients) Diarrhea (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/9449270/
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: https://pubmed.ncbi.nlm.nih.gov/10090425/	unhealthy, adult n = 86 Health Status: unhealthy Condition: lower respiratory tract infections or sexually transmitted infections Age Group: adult Sex: M+F Population Size: 86 Sources: https://pubmed.ncbi.nlm.nih.gov/10090425/	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea (1.2%) Vomiting (1.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/10090425/
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10090425/	unhealthy, adult n = 1069 Health Status: unhealthy Condition: lower respiratory tract infections or sexually transmitted infections Age Group: adult Sex: M+F Population Size: 1069 Sources: https://pubmed.ncbi.nlm.nih.gov/10090425/	Disc. AE: Bad taste, Nausea... AEs leading to discontinuation/dose reduction: Bad taste (0.3%) Nausea (0.8%) Vomiting (0.6%) Headache (0.3%) Dizziness (0.5%) Rash (0.2%) Tachycardia (<0.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/10090425/
600 mg 1 times / day steady, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10090425/	unhealthy, adult n = 1406 Health Status: unhealthy Condition: lower respiratory tract infections or sexually transmitted infections Age Group: adult Sex: M+F Population Size: 1406 Sources: https://pubmed.ncbi.nlm.nih.gov/10090425/	Disc. AE: Bad taste, Nausea... AEs leading to discontinuation/dose reduction: Bad taste (1%) Nausea (2.6%) Vomiting (1.4%) Headache (0.6%) Dizziness (0.6%) Rash (0.6%) Tachycardia (0.14%) Sources: https://pubmed.ncbi.nlm.nih.gov/10090425/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 OCTN2 66	MRP2 205 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19951720/	yes
OCTN2 71	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16928358/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP2 205	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11796340/	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11796340/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/11125032/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY510763	https://www.001chemical.com/chem/119914-60-2
3B Scientific (Wuhan) Corp	3B2-1175	http://www.3bsc.com/index/pro_info.php?id=54891
Ambeed	A250293	https://www.ambeed.com/products/119914-60-2.html
Ambinter	Amb20243294	http://www.ambinter.com/reference/20243294
Ark Pharma Scientific Limited	A-0456	http://www.arkpharmtech.com/product/32407.html
BLD Pharm	BD132389	http://www.bldpharm.com/products/119914-60-2.html
BLD Pharm	BD58087	http://www.bldpharm.com/products/146863-02-7.html
BioChemPartner	BCP23880	http://www.biochempartner.com/119914-60-2-BCP23880
ChemMol	99045115	http://www.chemmol.com/chemmol/99045115.html
Finetech	FT-0703068	http://www.finetechnology-ind.com/prod/detail/pub/119914-60-2.html
Lab Network	LN01294778	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01294778
MolPort	MolPort-006-167-530	https://www.molport.com/shop/molecule-link/MolPort-006-167-530
Molcore	MC510763	https://www.molcore.com/product/119914-60-2
MuseChem	M096992	https://www.musechem.com/product/M096992.html
Smolecule	S587758	https://www.smolecule.com/products/s587758
THE BioTek	bt-318580	https://www.thebiotek.com/product/others/bt-318580
eNovation Chemicals	Y0974187	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0974187
iChemical	EBD53618	http://www.ichemical.com/products/119914-60-2.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
[In vitro anti-MAC activities of new quinolones in focus (2)].	1996 Sep	8999137
[In vitro anti-MAC activities of new quinolones in focus (1)].	1996 Sep	8999136
Comparative antimycobacterial activities of ofloxacin, ciprofloxacin and grepafloxacin.	1999 Nov	10552981
Anti-toxoplasma activities of 24 quinolones and fluoroquinolones in vitro: prediction of activity by molecular topology and virtual computational techniques.	2000 Oct	10991859
Prediction of quinolone activity against Mycobacterium avium by molecular topology and virtual computational screening.	2000 Oct	10991858
In vitro activities of six fluoroquinolones against 250 clinical isolates of Mycobacterium tuberculosis susceptible or resistant to first-line antituberculosis drugs.	2000 Sep	10952620
Fluoroquinolones as chemotherapeutics against mycobacterial infections.	2004	15544510
Mycobacterium tuberculosis DNA gyrase: interaction with quinolones and correlation with antimycobacterial drug activity.	2004 Apr	15047530
Multidrug resistance-associated protein 1 functions as an efflux pump of xenobiotics in the skin.	2005 Jun	15948026
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.	2010 Dec	21158687

Patents

Sample Use Guides

In Vivo Use Guide

RAXAR (Grepafloxacin) Tablets may be taken with or without meals. The usual dose for RAXAR is 400 mg or 600 mg orally every 24 hours. Sucralfate; antacids containing magnesium, calcium, or aluminum; multivitamins containing iron or zinc; or VIDEX (didanosine) chewable/buffered tablets or the pediatric powder for oral solution should not be taken within 4 hours before or 4 hours after taking grepafloxacin.

Route of Administration: Oral

In Vitro Use Guide

The activity of grepafloxacin was evaluated against five isolates of Chlamydia pneumonia and 21 isolates of Chlamydia trachomatis. MICs were determined using a tissue culture incorporation technique in McCoy cell monolayers treated with Grepafloxacin. After 48–72 h incubation, cover slips were fixed in methanol and stained with an immunofluorescent monoclonal antibody against the major outer membrane protein. Grepafloxacin MIC range was 0.06–0.12 mg/L.

Name

Type

Language

GREPAFLOXACIN

Official Name

English

3-QUINOLINECARBOXYLIC ACID, 1-CYCLOPROPYL-6-FLUORO-1,4-DIHYDRO-5-METHYL-7-(3-METHYL-1-PIPERAZINYL)-4-OXO-, (±)-

Common Name

English

Grepafloxacin [WHO-DD]

Common Name

English

3-QUINOLINECARBOXYLIC ACID, 1-CYCLOPROPYL-6-FLUORO-1,4-DIHYDRO-5-METHYL-7-(3-METHYL-1-PIPERAZINYL)-4-OXO-

Systematic Name

English

(±)-1-CYCLOPROPYL-6-FLUORO-1,4-DIHYDRO-5-METHYL-7-(3-METHYL-1-PIPERAZINYL)-4-OXO-3-QUINOLINECARBOXYLIC ACID

Systematic Name

English

GREPAFLOXACIN [MI]

Common Name

English

grepafloxacin [INN]

Common Name

English

GREPAFLOXACIN [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C795