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1 Grepafloxacin is a new oral fluoroquinolone with potent activity against community acquired respiratory pathogens, including Streptococcus pneumoniae, and pharmacokinetic properties which allow once daily dosing. As part of its safety evaluation a study of 4 weeks duration was performed to compare the toxicity of grepafloxacin with that of a number of commercially available quinolones in the rat.    2 Groups of eight male Sprague-Dawley rats received either control material or grepafloxacin, enoxacin, lomefloxacin, ofloxacin or ciprofloxacin at an oral dosage of 300 mg/kg/day for 4 consecutive weeks.    3 Effects related to the antibacterial activity of the drugs were seen as increased caecal weight, decreased urinary excretion of sodium, increased water consumption, decreased urine volume, increased urine osmolality, soft stools and suppressed body weight gain.    4 It is well documented that fluoroquinolones can cause lesions in the cartilage of the major diarthrodial joints, and blister formation or erosion on the joint surface was observed in all quinolone-treated groups other than the grepafloxacin group.    5 Some quinolones, have been found to cause crystal-luria, which is often associated with secondary nephropathy in laboratory animals due to the poor solubility of quinolones under the alkaline conditions of the urine. In the present study, needle-like crystals in the urinary sediment were observed in enoxacin and ciprofloxacin treated groups only.    6 In conclusion, grepafloxacin was well tolerated and showed a low potential for joint toxicity and crystalluria compared to other quinolones.

A comparative study of the repeat dose toxicity of grepafloxacin and a number of other fluoroquinolones in rats