Ophthalmotoxicity and ototoxicity of the new quinolone antibacterial agent levofloxacin in Long Evans rats.
An ophthalomo- and ototoxicity study of a new quinolone antibacterial agent, (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was investigated in Long Evans rats. The rats were orally administered 100 mg/kg of DR-3355, ciprofloxacin (CPFX), norfloxacin (NFLX) or nalidixic acid (NA) for 2 weeks, and the effects on visual and auditory functions were examined. Examination of electroretinograms (ERGs) revealed a decrease in the amplitudes of the a- and b-waves, a prolongation of the latency and diminution or disappearance of oscillatory potential waves in NA treated rats. Similar but milder changes were also noted in the NFLX treated rats. ERGs from DR-3355 or CPFX treated rats were normal. Histopathological examination revealed no changes suggestive of ophthalmotoxicity or ototoxicity in the rats treated with DR-3355, CPFX or NFLX. On the other hand, NA treated rats showed partial loss of the outer hair cells of the organ of Corti in the cochlea, suggesting that NA had slight ototoxicity. DR-3355 did not show any deleterious visual or auditory effects at the dose used in this study.
Nomura
M
M
Drug Safety Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Yamada
M
M
Yamamura
H
H
Kajimura
T
T
Takayama
S
S
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D004596:Electroretinography; D005128:Eye Diseases / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D006309:Hearing / Q000187:drug effects; D006311:Hearing Disorders / Q000139:chemically induced* / Q000473:pathology; D064704:Levofloxacin; D008297:Male; D015242:Ofloxacin / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000187:drug effects; D014785:Vision, Ocular / Q000187:drug effects
D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin