Norfloxacin hydrochloride
[CAS# 68077-27-0]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Quinolone
• Name: Norfloxacin hydrochloride
• Synonyms: 1-ethyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid hydrochloride
• Molecular Formula: C₁₆H₁₉ClFN₃O₃
• Molecular Weight: 355.79
• CAS Registry Number: 68077-27-0
• SMILES: CCN1C=C(C(=O)C2=CC(=C(C=C21)N3CCNCC3)F)C(=O)O.Cl

Properties

• Solubility: 45mg/mL (DMSO) (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H319
• Safety Statements: P264-P280-P305+P351+P338-P337+P313

Discovery and Applications

Norfloxacin hydrochloride is a synthetic fluoroquinolone antibiotic used in the treatment of bacterial infections. It is the hydrochloride salt form of norfloxacin, which enhances its solubility and stability for pharmaceutical formulations. The compound exhibits broad-spectrum antibacterial activity, particularly against Gram-negative aerobic pathogens, and functions by inhibiting bacterial DNA gyrase and topoisomerase IV, enzymes essential for DNA replication and transcription.

Norfloxacin was developed in the late 1970s by Kyorin Pharmaceutical Co., Ltd., in Japan and was one of the earliest fluoroquinolone antibiotics introduced to clinical use. The discovery was a result of structural modification of nalidixic acid, an earlier quinolone antibiotic. By introducing a fluorine atom at the C-6 position and a piperazine ring at the C-7 position of the quinolone core, researchers significantly improved the antibacterial potency and expanded the spectrum of activity of the molecule. The hydrochloride salt form was developed to facilitate manufacturing and improve the pharmacokinetic properties for oral administration.

Norfloxacin hydrochloride has been widely used in the treatment of urinary tract infections, prostatitis, gonorrhea, and gastrointestinal infections caused by susceptible strains of bacteria. It is especially effective against *Escherichia coli*, *Klebsiella pneumoniae*, *Proteus mirabilis*, *Pseudomonas aeruginosa*, *Neisseria gonorrhoeae*, *Shigella spp.*, and *Salmonella spp.* Due to its limited systemic absorption, it has also been employed in the management of local infections where high urinary concentrations are advantageous.

The mechanism of action of norfloxacin involves the inhibition of bacterial DNA gyrase and topoisomerase IV. These enzymes are responsible for introducing negative supercoils into bacterial DNA and facilitating chromosomal segregation during cell division. Inhibition of these targets leads to impaired DNA synthesis and ultimately results in bacterial cell death. The bactericidal effect is concentration-dependent, and resistant strains often emerge through mutations in the genes encoding these enzymes or by efflux mechanisms.

Pharmacokinetically, norfloxacin hydrochloride is administered orally and reaches peak plasma concentrations within 1 to 2 hours. However, its systemic bioavailability is moderate, and approximately 30–40% of the administered dose is absorbed. It is widely distributed in tissues and fluids, with a notable ability to concentrate in the urinary tract. The majority of the drug is excreted unchanged in the urine, making it suitable for treating infections of the lower urinary system.

Over time, the use of norfloxacin hydrochloride has declined due to the emergence of bacterial resistance and the availability of newer fluoroquinolones with improved pharmacokinetic and safety profiles. Nonetheless, it remains listed in many pharmacopeias and is available in several countries. It has also been used in veterinary medicine for treating infections in livestock and companion animals.

Norfloxacin hydrochloride has been formulated into tablets and ophthalmic solutions. In ophthalmology, norfloxacin drops have been utilized to treat bacterial conjunctivitis and other ocular infections. Its safety profile includes possible side effects such as gastrointestinal discomfort, dizziness, and photosensitivity. In rare cases, fluoroquinolones including norfloxacin have been associated with tendon rupture, peripheral neuropathy, and central nervous system effects.

Regulatory guidelines and quality specifications for norfloxacin hydrochloride are detailed in international pharmacopeias such as the USP and JP. These include parameters such as identification tests, assay methods, impurity profiles, and dissolution testing. The stability of the hydrochloride form under controlled storage conditions has been well-established, contributing to its shelf life and effectiveness in final dosage forms.

Norfloxacin hydrochloride represents a significant advancement in quinolone antibiotic development and has contributed to the broader understanding and clinical use of fluoroquinolones. Its discovery and clinical application mark an important chapter in the treatment of bacterial infections, particularly those resistant to older antibiotics.

References

2001. The fungus Pestalotiopsis guepini as a model for biotransformation of ciprofloxacin and norfloxacin. Applied Microbiology and Biotechnology, 57(1).
DOI: 10.1007/s002530100672

2019. Fluoroquinolones structural and medicinal developments (2013-2018): Where are we now? Bioorganic & Medicinal Chemistry, 27(14).
DOI: 10.1016/j.bmc.2019.05.038

2023. Metabolic variation and oxidative stress response of blue mussels (Mytilus sp.) perturbed by norfloxacin exposure. Environmental Science and Pollution Research International, 30(26).
DOI: 10.1007/s11356-023-27599-6