LD50 value, phototoxicity and convulsion induction test of the new quinolone antibacterial agent (S)-10-[(S)-(8-amino-6-azaspiro[3,4]octan-6-yl)]-9-fluoro-2, 3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxyl ic acid hemihydrate in laboratory animals.
(S)-10-[(S)-(8-Amino-6-azaspiro[3,4]octan-6-yl)]-9-fluoro-2, 3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxyli c acid hemihydrate (CAS 151390-79-3, DV-7751a) a new quinolone antibacterial agent, was examined for LD50 value, phototoxicity and convulsion inducing potential in laboratory animals. A single oral administration of DV-7751a induced soft stool in rats at 1000 and 2000 mg/ kg and in monkeys at 250 mg/kg and vomiting in monkeys at 500 mg/kg or more. A single intravenous administration caused a decrease in locomotor activity, respiratory depression, convulsion, pulmonary edema and death in rats and mice. The LD50 values with oral administration were more than 2000 mg/ kg for rats and mice and more than 250 mg/kg for monkeys, and those with intravenous administration were 164.3 mg/kg for rats of both sexes at an injection rate of 2 ml/min, 118.8 mg/kg for male rats and 104 to 125 mg/kg for female rats at 0.5 ml/min, and 184.7 mg/kg for male mice and 187.4 mg/kg for female mice. DV-7751a showed very weak phototoxicity in mice after single oral administration of 600 mg/kg, followed by UVA irradiation, but no convulsion after oral administration of 200 or 1000 mg/kg in combination with 4-biphenylacetic acid at 400 mg/kg.
Shimoda
K
K
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Akahane
K
K
Nomura
M
M
Kato
M
M
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003292:Convulsants / Q000633:toxicity*; D017484:Dermatitis, Phototoxic / Q000473:pathology*; D005260:Female; D024841:Fluoroquinolones; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D015242:Ofloxacin / Q000633:toxicity; D010648:Phenylacetates / Q000494:pharmacology; D015363:Quinolones / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003292:Convulsants; D024841:Fluoroquinolones; D010648:Phenylacetates; D015363:Quinolones; C084755:DV 7751a; C012776:biphenylylacetic acid; D015242:Ofloxacin