Prulifloxacin

Overview

Prulifloxacin is an older synthetic antibiotic of the fluoroquinolone class undergoing clinical trials prior to a possible NDA (New Drug Application) submission to the U.S. Food and Drug Administration (FDA). It is a prodrug which is metabolized in the body to the active compound ulifloxacin. It was developed over two decades ago by Nippon Shinyaku Co. and was patented in Japan in 1987 and in the United States in 1989.[1–5] WP

It has been approved for the treatment of uncomplicated and complicated urinary tract infections, community-acquired respiratory tract infections in Italy and gastroenteritis, including infectious diarrheas, in Japan. Prulifloxacin has not been approved for use in the United States.[3][6] WP

Risks and side effects

Contraindications

There are only four contraindications found within the package insert:[7] WP

• "Avoid using Prulifloxacin in elderly population (Risk of Tendon damage)."[7] WP
• "Prulifloxacin is contraindicated in patients with anamnesis of tendon diseases related to the administration of quinolones."[7] WP
• "Prulifloxacin is contraindicated in persons with a history of hypersensitivity to Prulifloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components."[7] WP
• "Prulifloxacin is contraindicated in subjects with celiac disease."'[7] WP
• "Prulifloxacin is also considered to be contraindicated within the pediatric population, pregnancy, nursing mothers, and in patients with epilepsy or other seizure disorders."[7] WP

Overdose

In the event of acute overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage; the patient should be carefully observed and given supportive treatment.[7] WP

Interactions

Interactions

• Probenecid: Prulifloxacin urinary excretion decreases when concomitantly administered with probenecid.[7] WP
• Fenbufen: The concomitant administration of fenbufen can cause increased risk of convulsions.[7] WP
• Hypoglycemic agents: May cause hypoglycemia in diabetic patients under treatment with hypoglycemic agents.[7] WP
• Theophylline: May cause a decreased theophylline clearance.[7] WP
• Warfarin: May enhance the effects of oral anticoagulants such as warfarin and its derivatives.[7] WP
• Nicardipine: May potentiate the phototoxicity of prulifloxacin.[7] WP

Pharmacology

Mechanism of action

Like other fluoroquinolones, Prulifloxacin prevents bacterial DNA replication, transcription, repair and recombination through inhibition of bacterial DNA gyrase. WP

Quinolones and fluoroquinolones are bactericidal drugs, eradicating bacteria by interfering with DNA replication. WP

Quinolones are synthetic agents that have a broad spectrum of antimicrobial activity as well as a unique mechanism of action, resulting in inhibition of bacterial DNA gyrase and topoisomerase IV. Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription. For many gram-negative bacteria, DNA gyrase is the target, whereas topoisomerase IV is the target for many gram-positive bacteria. It is believed that eukaryotic cells do not contain DNA gyrase or topoisomerase IV. WP

Pharmacokinetics

Prulifloxacin 600 mg achieves peak plasma concentration (Cmax) of ulifloxacin (1.6μg/mL) in a median time to Cmax (tmax) of 1 hour. Ulifloxacin is ≈45% bound to serum proteins in vivo. It is extensively distributed throughout tissues and shows good penetration into many body tissues. The elimination half-life (t1/2) of ulifloxacin after single-dose prulifloxacin 300–600 mg ranged from 10.6 to 12.1 hours. After absorption from the gastrointestinal tract, prulifloxacin undergoes extensive first-pass metabolism (hydrolysis by esterases, mainly paraoxonase to form ulifloxacin, the active metabolite). Unchanged ulifloxacin is predominantly eliminated by renal excretion. Quoting from the available package insert.[7] WP

History

History

In 1987 a European patent for prulifloxacin was issued to the Japanese-based pharmaceutical company, Nippon Shinyaku Co., Ltd (Nippon). Ten years after the issuance of the European patent, marketing approval was applied for and granted in Japan (March 1997). Subsequent to being approved by the Japanese authorities in 1997 prulifloxacin was co-marketed and jointly developed in Japan with Meiji Seika as licensee (Sword). WP

In more recent times, Angelini ACRAF SpA, under license from Nippon Shinyaku, has fully developed prulifloxacin, for the European market. Angelini is the licensee for the product in Italy. Following its launch in Italy, Angelini launched prulifloxacin in Portugal (January 2007) and it has been stated that further approvals will be sought in other European countries.[8][9][10] WP

Prulifloxacin is marketed in Japan and Italy as Quisnon (Nippon Shinyaku); Sword (Meiji); Unidrox (Angelini); Prixina (Angelini) and Glimbax (ITF Hellas) in Greece and generic as Pruquin. WP

In 1989 and 1992 United States patents (US 5086049) were issued to Nippon Shinyaku for prulifloxacin. It was not until June 2004, when Optimer Pharmaceuticals acquired exclusive rights to discover, develop and commercialize prulifloxacin (Pruvel) in the U.S. from Nippon Shinyaku Co., Ltd., that there were any attempts to seek FDA approval to market the drug in the United States. Optimer Pharmaceuticals expects to file an NDA (new drug application) for prulifloxacin some time in 2010. As the patent for prulifloxacin has already expired, Optimer Pharmaceuticals has stated that this may have an effect on the commercial prospects of prulifloxacin within the United States market.[11] WP

Chemistry

Formula

C21H20FN3O6S PC

CAS number

123447-62-1 PC

Molar mass (g/mol)

461.5 PC

IUPAC name (computed by PubChem)

6-fluoro-1-methyl-7-[4-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl]piperazin-1-yl]-4-oxo-1H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid PC

SMILES

CC1N2C3=CC(=C(C=C3C(=O)C(=C2S1)C(=O)O)F)N4CCN(CC4)CC5=C(OC(=O)O5)C PC

InChIKey

PWNMXPDKBYZCOO-UHFFFAOYSA-N PC

PubChem CID

65947

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Nelson JM, Chiller TM, Powers JH, Angulo FJ. Food Safety: Fluoroquinolone-Resistant Campylobacter Species and the Withdrawal of Fluoroquinolones from Use in Poultry: A Public Health Success Story. Clinical Infectious Diseases. 2007. doi:10.1086/512369 · PMID 17342653
2. Journal / agency Kawahara S. Chemotherapeutic agents under study. Nippon Rinsho. 1998. PMID 9883617
3. Journal / agency Fritsche TR, Biedenbach DJ, Jones RN. Antimicrobial Activity of Prulifloxacin Tested against a Worldwide Collection of Gastroenteritis-Producing Pathogens, Including Those Causing Traveler's Diarrhea. Antimicrobial Agents and Chemotherapy. 2008. doi:10.1128/AAC.01260-08 · PMID 19114678 · PMC2650572
4. Journal / agency Giannarini G, Tascini C, Selli C. Prulifloxacin: clinical studies of a broad-spectrum quinolone agent. Future Microbiology. 2009. doi:10.2217/17460913.4.1.13 · PMID 19207096
5. Other Ref patent
6. Journal / agency Anonymous. Prulifloxacin ['Quisnon'; Nippon Shinyaku] has been approved in Japan. Inpharma. 2002
7. Other Prulifloxacin Tablets. link 2
8. Other Research and Development Department of Angelini. Angelinipharma.com. Retrieved on 2010-11-03. link 2
9. Other Nippon Shinyaku, Annual Report 2007. link 2
10. Journal / agency Prulifloxacin. NAD-441A, NM 441, Quisnon. Drugs in R&D. 2002. doi:10.2165/00126839-200203060-00013 · PMID 12516950
11. Other Annual Report 2008, p. 34

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