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Quinolone toxicity: methods of assessment
1Drug Safety Evaluation, Abbott Laboratories, Abbott Park, Illinois 60064.
The American Journal of Medicine
|December 30, 1991
Summary
Fluoroquinolones offer improved antimicrobial activity and safety over older quinolones. Preclinical toxicity studies in animals show some joint, kidney, eye, and CNS effects, but these are generally not problematic in human use.
Area of Science:
- Pharmacology
- Toxicology
- Infectious Diseases
Background:
- Fluoroquinolones represent a significant advancement over older quinolone antibiotics.
- They exhibit broader antimicrobial spectra, enhanced pharmacokinetics, and improved clinical efficacy.
- Preclinical toxicity evaluations draw upon existing quinolone data regarding juvenile joints, kidneys, eyes, and the central nervous system (CNS).
Purpose of the Study:
- To review and summarize the preclinical toxicity findings of fluoroquinolones.
- To compare fluoroquinolone toxicity with that of earlier quinolone agents.
- To assess the relevance of animal toxicity data to human safety.
Main Methods:
- Review of animal studies investigating fluoroquinolone toxicity (norfloxacin, ciprofloxacin, ofloxacin, temafloxacin).
- Analysis of reported effects on juvenile joints, kidneys, eyes, and CNS.
- Comparison of fluoroquinolone findings with historical quinolone data.
Main Results:
- Fluoroquinolones, like quinolones, can cause arthropathic damage in young animals.
- Renal effects (nephritis, crystalluria) are likely due to precipitation in alkaline urine, posing less risk in humans.
- Ocular toxicity observed in animals (e.g., lenticular opacities) does not appear to be a significant issue in human use.
- CNS effects, including convulsions with specific drug combinations, are noted in both animals and humans.
Conclusions:
- Fluoroquinolone toxicity profiles in preclinical studies show some similarities to older quinolones, particularly regarding joint effects.
- Kidney and ocular toxicities observed in animals are generally considered less relevant to human clinical use.
- While CNS effects warrant attention, fluoroquinolones are generally considered safe and effective, representing an improvement over previous agents.