COMPARATIVE CHARACTERISTICS OF THE TOXIC EFFECTS OF FLUOROQUINOLONES

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DOI: https://doi.org/None
Issue: 
7
Year: 
2017

O.I. Avdeeva, PhD; M.N. Makarova, MD; V.G. Makarov, MD; D.V. Shubin; M.S. Simanovskaya; P.V. Burenkov Pharmacy House Research-and-Production Association; 245, Kuzmolovsky Urban-Type Settlement, Vsevolozhsky District, Leningrad Region 188663, Russian Federation

Introduction. The bactericidal effect of fluoroquinolones is due to the inhibition of the vital microbial cell enzymes DNA gyrase and topoisomerase IV, resulting in impaired DNA synthesis. Data on the toxicity of different fluoroquinolone generations are fragmented and fail to give a full view of the benefit-risk ratio in the representatives of different generations. Objective: to investigate the toxicity of some representatives of first-, second-, third-, and fourth-generation fluoroquinolones and to evaluate their safety during single and repeated administrations. Material and methods. Drugs from the group of fluoroquinolones, such as ciprofloxacin, levofloxacin, and moxifloxacin (in different dosage forms), were investigated on male and female outbred rats weighing 200-300 g. The drugs were intragastrically and intravenously administered. During the experiments, the weights of the animals and their individual organs were recorded; hematological and biochemical parameters were measured; histological examinations were performed. The individual behavior of the rats was studied in the open field test. Results. Moxifloxacin (a fourth generation) has statistically significant less pronounced toxic properties against the major target organs/tissues (of the central nervous system, kidneys, and liver). During their single use, second-, third-, and fourth-generation fluoroquinolones were equitoxic. During repeated administration, fourth-generation fluoroquinolones have less pronounced toxic properties than the representatives of second- and third- generations. Conclusion. Preclinical evaluation of the toxicity of representatives of various fluoroquinolone generations during single and repeated administrations has shown that the drugs are lowly toxic, have toxic effects on the laboratory animals when they are both intragastrically and intravenously administered at doses that are far higher than the therapeutic ones.
Keywords: 
fluoroquinolones
ciprofloxacin
levofloxacin
moxifloxacin
toxicity
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