[Five-week subacute intravenous toxicity study of cefodizime sodium in dogs].
A subacute toxicity study of cefodizime sodium (THR-221), a new cephem antibiotics, was carried out using male and female beagle dogs. THR-221 was intravenously administered to the dog at dose levels of 500, 1000 and 2000 mg/kg/day for 5 weeks, followed by 4 weeks recovery period. Cefotetan (CTT) as a reference drug was administered in the same manner at a dose level of 2000 mg/kg/day. The summarized results obtained are as follows: 1. Vomiting and salivation were observed in dogs given 1000 and 2000 mg/kg/day of THR-221. However, it caused no deaths or significant effects on body weight and food consumption in all groups treated with THR-221. 2. No toxicological changes associated with the administration of THR-221 were found in urinary and hematological examinations. 3. In serum biochemical examinations, increase or tendencies of increase of albumin and A/G ratio, probably due to the antibacterial action of THR-221, were detected at all dose levels of THR-221. 4. There were no dose-related changes in hepatic and renal function, fecal occult blood, ophthalmological, electrocardiographic and auditory examinations, absolute and relative organ weights. 5. Histopathological examinations revealed fibrosis or granulation in perivascular area of injection sites, particularly in males given 2000 mg/kg/day of THR-221. 6. After 4 weeks of recovery period, above-mentioned changes were generally disappeared and it was suggested that these were reversible ones. 7. In groups treated with CTT (2000 mg/kg/day), damages were recognized mainly in erythron values, liver and kidney, as compared with the same dose of THR-221. Therefore the toxicity of THR-221 was less than that of CTT. 8. From these results, the non toxic effective dose level and the toxic dose level of THR-221 were estimated to be 500 mg/kg/day and more than 2000 mg/kg/day respectively, for male and female dogs.
Nakano
S
S
Drug Safety Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Yada
H
H
Irimura
K
K
Kurokawa
K
K
Hirota
T
T
Morita
K
K
D000818:Animals; D002439:Cefotaxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D015313:Cefotetan / Q000008:administration & dosage / Q000633:toxicity; D004285:Dogs; D005260:Female; D005355:Fibrosis; D006097:Granulation Tissue / Q000187:drug effects / Q000473:pathology; D007275:Injections, Intravenous; D008297:Male; D012472:Salivation / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism; D012712:Serum Globulins / Q000378:metabolism; D014680:Veins / Q000187:drug effects / Q000473:pathology; D014839:Vomiting / Q000139:chemically induced
D012709:Serum Albumin; D012712:Serum Globulins; D015313:Cefotetan; D002439:Cefotaxime; C033356:cefodizime