药品详细

Trovafloxacin(曲伐沙星)

基本信息
剂型规格
适应症
药理
临床
理化性质
相互作用
文档
专利
Pathway
文献
序列

化学结构式图

中文名

曲伐沙星

英文名

Trovafloxacin

分子式

C₂₀H₁₅F₃N₄O₃

化学名

7-[(1R,5S)-6-amino-3-azabicyclo[3.1.0]hexan-3-yl]-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid

分子量

Average: 416.3533
Monoisotopic: 416.109624981

CAS号

147059-72-1

ATC分类

J01M 未知

药物类型

small molecule

阶段

approved

商品名

Trovan;

同义名

Trovafloxacin mesylate;TVFX;

基本介绍

Trovafloxacin (sold as Trovan by Pfizer) is a broad spectrum antibiotic that inhibits the uncoiling of supercoiled DNA in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It was withdrawn from the market due to the risk of hepatotoxicity. It had better gram-positive bacterial coverage and less gram-negative coverage than the previous fluoroquinolones. [Wikipedia]

生产厂家

Pfizer central research
Pfizer chemicals div pfizer inc

封装厂家

Pfizer Inc.

参考

Synthesis Reference	Not Available
General Reference	Not Available

剂型

规格

化合物类型

Type	small molecule

Classes

Fluoroquinolones and Quinolones

Substructures

Hydroxy Compounds
Acetates
Aliphatic and Aryl Amines
Pyridines and Derivatives
Cyclopropane and Derivatives
Pyrrolidines
Benzene and Derivatives
Carboxylic Acids and Derivatives
Aminopyridines and Derivatives
Halobenzenes
Heterocyclic compounds
Aromatic compounds
Cyanamides
Aryl Halides
Anilines
Piperidines
Fluoroquinolones and Quinolones

适应症

antibacterials 抗细菌;

药理

Indication

For treatment of infections caused by susceptible strains of the designated microorganisms in uncomplicated urethral gonorrhea in males and endocervical and rectal gonorrhea in females caused by Neisseria gonorrhoeae as well as non gonoccocal urethritis and cervicitis due to Chlamydia trachomatis.

Pharmacodynamics

Trovafloxacin is a broad spectrum antibiotic that inhibits DNA supercoiling in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It is not used widely due to the risk of hepatotoxicity. It tends to have better gram-positive bacterial coverage and less gram-negative coverage than the previous fluoroquinolones. Mechanism of action of fluoroquinolones including trovafloxacin is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines. Therefore fluoroquinolones may be active against pathogens that are resistant to these antibiotics. There is no cross-resistance between trovafloxacin and the mentioned classes of antibiotics. The overall results obtained from in vitro synergy studies, testing combinations of trovafloxacin with beta-lactams and aminoglycosides, indicate that synergy is strain specific and not commonly encountered. This agrees with results obtained previously with other fluoroquinolones. Resistance to trovafloxacin in vitro develops slowly via multiple-step mutation in a manner similar to other fluoroquinolones. Resistance to trovafloxacin in vitro occurs at a general frequency of between 1x10^-7 to 10^-10. Although cross-resistance has been observed between trovafloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to trovafloxacin.

Mechanism of action

Trovafloxacin is a fluoronaphthyridone related to the fluoroquinolones with in vitro activity against a wide range of gram-negative and gram-positive aerobic and anaerobic microorganisms. The bactericidal action of trovafloxacin results from inhibition of DNA gyrase and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription, and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division.

Absorption

Well-absorbed from the gastrointestinal tract after oral administration and does not depend on concomitant food intake. The absolute bioavailability is approximately 88%.

Volume of distribution

Not Available

Protein binding

The mean plasma protein bound fraction is approximately 76%, and is concentration-independent.

Metabolism

Metabolism Trovafloxacin is metabolized by conjugation (the role of cytochrome P450 oxidative metabolism of trovafloxacin is minimal). The major metabolites include the ester glucuronide, which appears in the urine (13% of the administered dose); and the N -acetyl metabolite, which appears in the feces and serum (9% and 2.5% of the administered dose, respectively). Other minor metabolites include diacid, hydroxycarboxylic acid, and sulfamate, which have been identified in both the feces and the urine in small amounts (< 4% of the administered dose).

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate	Enzymes	Product
Trovafloxacin		Sulfamate	Details

Route of elimination

Approximately 50% of an oral dose is excreted unchanged (43% in the feces and 6% in the urine).

Half life

Following oral administration, half-life ranged from 9.1 hours to 12.2 hours over the dosage range of 100 to 200 mg tablets. Following intravenous infusion, half-life ranged from 9.4 to 12.7 hours over a dosage range of 100 to 300 mg.

Clearance

Not Available

Toxicity

Symptoms of overdose include convulsions, decreased activity, diarrhea, sleepiness, tremors, and/or vomiting.

Affected organisms

Enteric bacteria and other eubacteria

Pathways

Not Available

理化性质

Properties

State

solid

Experimental Properties

Property	Value	Source
water solubility	12.3 mg/L (at 25 °C)	MCFARLAND,JW ET AL. (2001)
logP	0.31	DAYLIGHT (2002)

Predicted Properties

Property	Value	Source
water solubility	7.04e-02 g/l	ALOGPS
logP	0.86	ALOGPS
logP	0.14	ChemAxon
logS	-3.8	ALOGPS
pKa (strongest acidic)	5.41	ChemAxon
pKa (strongest basic)	9.44	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	7	ChemAxon
hydrogen donor count	2	ChemAxon
polar surface area	99.76	ChemAxon
rotatable bond count	3	ChemAxon
refractivity	101.04	ChemAxon
polarizability	38.34	ChemAxon

药物相互作用

Drug	Interaction
Aluminium	Aluminum may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the aluminum containing agent to minimize the interaction.
Calcium	Formation of non-absorbable complexes
Calcium Acetate	Calcium may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the calcium containining agent to minimize the interaction.
Calcium Chloride	Calcium may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the calcium containing agent to minimize the interaction.
Calcium Gluceptate	Calcium may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the calcium containing agent to minimize the interaction.
Didanosine	Didanosine may decrease the absorption of orally administered Trovafloxacin. The Didanosine formulation contains magnesium and aluminum ions that intefere with Trovafloxacin absorption. Administer Trovafloxacin 2 hours before or 6 hours after the Didanosine dose to minimize the interaction. This interaction is not observed with enteric coated Didanosine.
Iron	Iron may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the iron containing agent to minimize the interaction.
Iron Dextran	Formation of non-absorbable complexes
Magnesium	Formation of non-absorbable complexes
Magnesium oxide	Magnesium may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the magnesium containing agent to minimize the interaction.
Magnesium Sulfate	Magnesium may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the magnesium containing agent to minimize the interaction.
Morphine	Morphine may reduce serum levels of Trovafloxacin decreasing the efficacy of the antibiotic. IV doses of morphine should be administered at least 2 hours after a dose of Trovafloxacin given in a fasting state or 4 hours after if given in a fed state.
Quinapril	Quinapril may decrease the absorption of orally administered Trovafloxacin. The Quinapril formulation contains magnesium ions that may intefere with Trovafloxacin absorption. Administer Trovafloxacin 2 hours before or 6 hours after the Quinapril dose to minimize the interaction.
Sevelamer	Sevelamer may decrease the absorption of orally administered Trovafloxacin. The Sevelamer formulation contains iron that may intefere with Trovafloxacin absorption. Administer Trovafloxacin 2 hours before or 6 hours after the Sevelamer dose to minimize the interaction.
Sucralfate	Sucralfate may decrease the absorption of orally administered Trovafloxacin. The Sucralfate formulation contains aluminum ions that may intefere with Trovafloxacin absorption. Administer Trovafloxacin 2 hours before or 6 hours after the Sucralfate dose to minimize the interaction.
Zinc	Zinc may decrease the absorption of orally administered Trovafloxacin. Administer Trovafloxacin 2 hours before or 6 hours after a dose of the zinc containing agent to minimize the interaction.

食物相互作用

Not Available

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