Norfloxacin nicotinate
[CAS# 118803-81-9]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Quinoline compound
• Name: Norfloxacin nicotinate
• Synonyms: 3-Pyridinecarboxylic acid mono[1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylate]
• Molecular Formula: C₁₆H₁₈FN₃O₃.C₆H₅NO₂
• Molecular Weight: 442.45
• CAS Registry Number: 118803-81-9
• EC Number: 629-941-0
• SMILES: CCN1C=C(C(=O)C2=CC(=C(C=C21)N3CCNCC3)F)C(=O)O.C1=CC(=CN=C1)C(=O)O

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

Norfloxacin nicotinate is a salt form of norfloxacin, a fluoroquinolone antibiotic that was developed in the late 1970s and introduced into clinical use in the early 1980s. Norfloxacin itself is a synthetic antimicrobial agent derived from nalidixic acid, and it is structurally characterized by a fluorine atom at position 6 and a piperazine ring at position 7 of the quinolone nucleus. These substitutions enhance its activity against a broad spectrum of Gram-negative and some Gram-positive bacteria. The nicotinate salt of norfloxacin is formed through the reaction of norfloxacin with nicotinic acid, resulting in a compound that retains the antibacterial activity of norfloxacin while potentially offering modified physicochemical properties such as improved solubility or altered absorption characteristics.

Norfloxacin nicotinate, like norfloxacin, functions by inhibiting bacterial DNA gyrase and topoisomerase IV, enzymes that are essential for DNA replication, transcription, and repair. This inhibition leads to the disruption of bacterial cell division and ultimately results in cell death. Norfloxacin exhibits concentration-dependent bactericidal activity, and its efficacy is closely related to the ratio of the peak drug concentration to the minimum inhibitory concentration (MIC) of the target pathogen.

Norfloxacin and its salt forms have been used primarily in the treatment of urinary tract infections, prostatitis, and gastrointestinal infections caused by susceptible bacterial strains. Norfloxacin nicotinate, as a formulation variant, has been developed to optimize drug delivery and pharmacokinetics, although the fundamental antibacterial activity is attributed to the norfloxacin component. Salt forms like the nicotinate may offer benefits such as enhanced aqueous solubility or improved oral bioavailability, depending on the pharmaceutical design, although such advantages must be substantiated by clinical and pharmacological data.

The pharmacokinetics of norfloxacin after oral administration involve moderate absorption, with peak plasma concentrations reached within one to two hours. The drug is eliminated primarily through renal excretion, with both unchanged drug and metabolites found in the urine. Norfloxacin is also excreted to a lesser extent in the feces. The pharmacological activity of norfloxacin in the urinary tract makes it particularly suitable for the treatment of infections localized in that region.

Adverse effects associated with norfloxacin include gastrointestinal symptoms such as nausea, abdominal discomfort, and diarrhea. Central nervous system effects such as dizziness, headache, and sleep disturbances have also been reported. In rare cases, serious adverse reactions such as tendonitis and tendon rupture, peripheral neuropathy, and QT interval prolongation have occurred, leading to updated warnings and prescribing guidelines. As with other fluoroquinolones, norfloxacin and its derivatives are used with caution in specific populations, including the elderly and individuals with predisposing factors for tendon injury.

Norfloxacin nicotinate represents a chemically modified form of a well-established antimicrobial agent, designed to potentially enhance pharmaceutical performance without altering the core mechanism of action. It is used in formulations where the nicotinate salt may provide manufacturing or pharmacological advantages. The antibacterial spectrum, clinical indications, and safety profile of norfloxacin nicotinate remain consistent with those of norfloxacin, underscoring the critical role of the parent compound in determining therapeutic efficacy.

References

2020. Effects of norfloxacin nicotinate on the early life stage of zebrafish (Danio rerio): Developmental toxicity, oxidative stress and immunotoxicity. Fish & Shellfish Immunology, 96.
DOI: 10.1016/j.fsi.2019.12.008

2014. Comparative pharmacokinetics of norfloxacin nicotinate in common carp (Cyprinus carpio) and crucian carp (Carassius auratus) after oral administration. Journal of Veterinary Pharmacology and Therapeutics, 38(3).
DOI: 10.1111/jvp.12193

1996. Norfloxacin nicotinate pharmacokinetics in unwearied and weaned calves. Journal of Veterinary Pharmacology and Therapeutics, 19(2).
DOI: 10.1111/j.1365-2885.1996.tb00025.x