FOUR-WEEK SUB-ACUTE TOXICITY STUDY 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 (DR-3355)IN CD RATS AND CYNOMOLGUS MONKEYS

• Published in: Journal of toxicological sciences Vol. 16; no. 1; pp. 29 - 48
• Main Authors: KATO, Michiyuki, WEST, Heather A, ASHBY, Roger, VIRGO, David M, FOWLER, John S L, FURUHAMA, Kazuhisa, TAKAYAMA, Satoshi
• Format: Journal Article
• Language: English
• Published: Tokyo The Japanese Society of Toxicology 1991; Japanese Society of Toxicology; Japan Science and Technology Agency
• Subjects: Animals; Biological and medical sciences; Blood Chemical Analysis; Body Weight - drug effects; Bone Marrow - drug effects; Bone Marrow Cells; Drug toxicity and drugs side effects treatment; Eating - drug effects; Female; Macaca fascicularis; Male; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); monkey; Ofloxacin - toxicity; Organ Size - drug effects; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Vertebrata; Mammalia; Rat; Toxicity; Animal; Rodentia; Monkey; Oral administration; Primates; Antibacterial agent; Subacute
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.16.29

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, DR-3355, a new quinolone antimicrobial agent, was administered by oral gavage to groups of ten male and ten female CD rats at dosages of 50, 200 or 800 mg/kg/day and to groups of three male and three female cynomolgus monkeys at dosages of 10, 30 or l00 mg/kg/day. Both species were treated for four weeks. The vehicle (0.5% sodium carboxymethyl cellulose)-treated group served as control. Rats at the high dose showed salivation, slight increases in total leucocyte and lymphocyte counts, slight changes in the plasma electrolyte balance, and minor reducions in urea concentration. The articular surfaces of the humerus and femur of rats at the high dose showed minor degenerative changes. Increased caecal weight occurred in rats at all the treatment groups. Monkeys at the high dose showed salivation, diarrhoea and lost weight. There was no microscopic change in the tissues examined. No effect levels under these conditions were established at 200 mg/kg/day in the rat, and 30 mg/kg/day in the monkey.