Twenty-six-week oral toxicity of the new quinolone antibacterial agent levofloxacin in rats and cynomolgus monkeys.
The oral 26-week toxicity of (-)-(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 rats and monkeys. Rats receiving higher doses of DR-3355 exhibited an increased number of larger fecal pellets, salivation, lower neutrophil counts, enlargement of the cecum and prominent goblet cells in the cecal mucosa. Monkeys did not show any changes due to DR-3355 treatment. Therefore, a no-effect dose of DR-3355 under these conditions was determined as 20 mg/kg in the rat and 62.5 mg/kg in the cynomolgus monkey.
Kato
M
M
Drug Safety Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Furuhama
K
K
Woolley
A P
AP
Ashby
R
R
Fowler
J S
JS
Takayama
S
S
D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000633:toxicity* / Q000652:urine; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004562:Electrocardiography; D005260:Female; D064704:Levofloxacin; D008252:Macaca fascicularis; D008297:Male; D015242:Ofloxacin / Q000097:blood / Q000633:toxicity* / Q000652:urine; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin