Quinolone toxicity: methods of assessment

Abstract

The newer quinolones, the fluoroquinolones, are represented by norfloxacin, ciprofloxacin, ofloxacin, and newer agents such as temafloxacin. These agents represent an improvement over their quinolone counterparts in many ways, including a wider spectrum of antimicrobial activity, improved pharmacokinetic properties, clinical efficacy against a wider range of diseases, and fewer and less severe adverse effects. The focus of preclinical evaluation of fluoroquinolone toxicity is guided by earlier data gathered from the quinolones on the juvenile joint, the kidney, the eye, and the central nervous system (CNS). Animal studies with the fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin, and temafloxacin) show similar arthropathic damage to the joints of young animals as did the earlier investigations with quinolones. Effects on the kidney that have been reported with quinolones and fluoroquinolones include mild interstitial nephritis, occult blood in urine, decreased renal function, increased renal weight, and crystalluria. These effects are not believed to be a direct toxic effect, but secondary to precipitation of foreign material in the kidney with a neutral or alkaline urine. Because human urine is not normally alkaline, related toxicities should theoretically not be a problem, and clinical data to date generally support this thesis. Ocular toxicity consisting of lenticular opacities in rats and dogs, electrical and histopathologic changes in cats, and electrical changes in dogs have been reported after fluoroquinolone administration; this toxicity does not appear to be a problem in human use. CNS effects have been noted in both animals and humans. Convulsions have been observed with concomitant administration of enoxacin and fenbufen.