Trovafloxacin

Thuốc trị ký sinh trùng, chống nhiễm khuẩn

Thuốc Gốc

Small Molecule

CAS: 147059-72-1

ATC: J01MA13

ĐG : Pfizer Inc. , http://www.pfizer.com

CTHH: C₂₀H₁₅F₃N₄O₃

PTK: 416.3533

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 It was withdrawn from the market due to the risk of hepatotoxicity.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]

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₀H₁₅F₃N₄O₃

Phân tử khối

416.3533

Monoisotopic mass

416.109624981

InChI

InChI=1S/C20H15F3N4O3/c21-8-1-2-15(13(22)3-8)27-7-12(20(29)30)17(28)9-4-14(23)19(25-18(9)27)26-5-10-11(6-26)16(10)24/h1-4,7,10-11,16H,5-6,24H2,(H,29,30)/t10-,11+,16?

InChI Key

InChIKey=WVPSKSLAZQPAKQ-SOSAQKQKSA-N

IUPAC Name

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

Traditional IUPAC Name

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

SMILES

[H][C@@]12CN(C[C@]1([H])C2N)C1=C(F)C=C2C(=O)C(=CN(C3=C(F)C=C(F)C=C3)C2=N1)C(O)=O

Độ hòa tan

12.3 mg/L (at 25 °C)

logP

0.31

logS

-3.8

pKa (strongest acidic)

5.41

pKa (Strongest Basic)

9.44

PSA

99.76 Å²

Refractivity

101.04 m³·mol^-1

Polarizability

38.34 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

Ghose Filter

true

Dược Lực Học : 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.

Cơ Chế Tác Dụng : 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] 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.

Dược Động Học :

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

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

Chỉ Định : 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.

Tương Tác Thuốc :

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.

Liều Lượng & Cách Dùng : Liquid - Intravenous
Tablet - Oral

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Pfizer

Sản phẩm biệt dược : Trovan

Đóng gói

Công ty : Pfizer Inc.

Website : http://www.pfizer.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB00685

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=62959

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508751

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C07664

ChemSpider

http://www.chemspider.com/Chemical-Structure.56670.html

BindingDB

http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50146361

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0049-3890-28

PharmGKB

http://www.pharmgkb.org/drug/PA164749184

Wikipedia

http://en.wikipedia.org/wiki/Trovafloxacin

RxList

http://www.rxlist.com/cgi/generic/trovazit.htm

Drugs.com

http://www.drugs.com/mtm/trovafloxacin.html

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