Toxicity of quinolone antimicrobial agents

Abstract

An approach to minimization of toxicity of a new compound is to elucidate the mechanisms of toxicity of analogous compounds and to clarify their structure-toxicity relationships. A problem with this approach, however, is that such elucidation remains difficult. For quinolones, some improvements in this mechanistic approach have been achieved in the central nervous system (CNS), particularly with regard to their interaction with non-steroidal anti-inflammatory drugs (NSAIDs), and in genotoxicity and phototoxicity studies, particularly in comparison with other toxicities, such as to the cardiovascular, gastrointestinal, bone, reproductive, and developmental systems. This review concentrates on a description of the known effects of quinolones on various organ systems in experimental animals and humans. Given the logarithmic increase in the synthesis of new quinolones, it is questionable whether these drugs share similar safety and efficacy. Nevertheless, this mechanistic approach to the investigation and minimization of toxicity has produced satisfactory results to date and deserves to be continued.

Toxicology of baytril (enrofloxacin)

“…A baytril 0.5% eye drop formulation, however, did not produce any irritation after application to the rabbit eyes (Altreuther, 1987). Studies on the effects of drug on the central nervous system showed only a weak stimulation of spontaneous motility after 100 mg/kg, but at a lower dose, there was no evidence of an influence exerted on the central nervous system (Takayama et al, 1995). In addition, no adverse effects were observed on the central nervous system (CNS) of mice, rats, dogs and cats.…”

“…In sub-chronic feeding studies of enrofloxacin as an active substance, the no-effect level (NOEL), which is the dose that can be administered with food over prolonged periods without adverse effects was determined (Altreuther, 1992). For rats, mice and adult dogs, general NOELs of 165, 550 and 52 mg/kg BW, respectively, were detected (Takayama et al, 1995;Altreuther, 1992). Without recognizable injury, both rats and dogs tolerated up to 2000 mg/kg of active ingredient feed (Boothe, 1994).…”

“…Enrofloxacin has undergone considerable toxicological and safety testing in laboratory species, such as mice, rats and guinea pigs, as well as in the target species, such as dog and cat (Takayama et al, 1995). In general, some side effects of quinolones on different organ systems (e.g.…”

A Non-Arthropathic Dose and Its Disposition Following Repeated Oral Administration of Ofloxacin, a New Quinolone Antimicrobial Agent, to Juvenile Dogs.

“…However, quinolones have been reported to induce arthropathy in juvenile animals such as mice [12], rats [4, 9, 10], rabbits [11], dogs [3, 5, 8, 20], nonhuman primates [17] and others [1, 2] as a class effect of these derivatives. Among these species, the juvenile dog is thought to be most susceptible to articular cartilage lesions [6,19,20].In our previous report [23], the arthropathic lesion due to ofloxacin was observed only in juvenile dogs, despite the fact that the drug concentration in the synovial fluid and articular cartilage of immature dogs (3-month-old) was equal to or lower than those in mature dogs (18-month-old). Kato and coworkers [10] have indicated that metabolically active immature chondrocytes are more sensitive to the effects of a quinolone, compared with inactive mature cells in the ex vivo study using 3 H-thymidine.…”

“…However, quinolones have been reported to induce arthropathy in juvenile animals such as mice [12], rats [4,9,10], rabbits [11], dogs [3,5,8,20], nonhuman primates [17] and others [1,2] as a class effect of these derivatives. Among these species, the juvenile dog is thought to be most susceptible to articular cartilage lesions [6,19,20].…”