Toxicity of quinolone antimicrobial agents.
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.
Takayama
S
S
Developmental Research Laboratories, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Hirohashi
M
M
Kato
M
M
Shimada
H
H
D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001842:Bone and Bones / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D002319:Cardiovascular System / Q000187:drug effects; D002356:Cartilage / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D004249:DNA Damage; D017484:Dermatitis, Phototoxic; D004064:Digestive System / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009153:Mutagens / Q000633:toxicity; D012098:Reproduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D013723:Teratogens / Q000633:toxicity
D042462:4-Quinolones; D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D009153:Mutagens; D013723:Teratogens