Comparison of organ-specific toxicity of temafloxacin in animals and humans.

This article summarizes animal studies conducted to determine the toxic and mutagenic potential of temafloxacin. The four target tissues of potential concern with fluoroquinolone use are the kidney, the eye, the weight-bearing joints of young animals, and the central nervous system. Based on the results of these studies in rats and dogs, it appears unlikely that crystalluria or nephrotoxicity will occur in humans who receive temafloxacin. Pre-marketing clinical trials in humans (n = 5,308) correlate well with chronic toxicity animal studies, reporting no crystalluria or clinically significant nephrotoxicity. Reversible electroretinographic (ERG) changes in dog studies were demonstrated only with the administration of high temafloxacin dosages. A Phase I study evaluating the safety of temafloxacin at 600 mg b.i.d. for 14 days in human subjects reported no significant changes in ophthalmologic parameters. Evidence of cartilaginous joint damage was observed in puppies receiving oral temafloxacin, in young dogs receiving intravenous temafloxacin, and in a single dog receiving a lethal dosage in a dose range-finding study. However, these toxic findings were not evident in any dogs in the subacute or chronic oral toxicity studies or in a longer duration intravenous study. Although limited evidence would suggest that young children may not be at risk, thorough clinical investigations of quinolones in these patients have only recently been initiated. Signs of central nervous system toxicity caused by temafloxacin were absent in two rodent studies, during which clonic convulsions were induced by concomitant use of fenbufen plus enoxacin or ciprofloxacin, and in human subjects evaluated by positron emission tomography. Temafloxacin, contrary to most other quinolones, was considered nonmutagenic in all mutagenicity tests conducted. In reproductive studies, temafloxacin was not uniquely toxic to the developing conceptus in the laboratory rat, mouse, rabbit, or primate. Based on these animal studies, temafloxacin appears to be non-mutagenic and to have a low potential for producing renal or ocular toxicity; however, like other quinolones, it should not be routinely used in children or pregnant women because of evidence of cartilage damage reported in young dogs. Premarketing clinical trials to date confirm the safety of temafloxacin use in adults.