1980 Volume 28 Issue Supplement6 Pages 189-219
Cefoperazone (CPZ, T-1551) is a newly developed cephalosporin antibiotic which has been demonstrated to be bactericidal not only against gram-positive bacteria but also against gram-negative bacteria, especially Pseudomonas and Enterobacter. The present study was conducted to evaluate the subacute and chronic toxicities of CPZ administered to rats daily by intraperitoneal injection. Rats (72 males, 72 females) divided into four CPZ groups at dose levels of 4000, 2000, 1000 and 500 mg/kg/day, a cephalothin (CET) group at dose level of 2000 mg/kg/day and a saline control group were injected intraperitoneally once a day, 7 day a week, for a month in the subacute toxicity. Rats (100 males, 100 females) divided into four CPZ groops at the above dose levels and a saline control group were injected 6 days a week, for six months in the chronic toxicity.
The results obtained are as follows:
1) Temporary writhing was observed immediately after injection in rats receiving the higher doses of CPZ and CET. Soft stool and diarrhea appeared sporadically in the same groups.
2) The body weight gain was depressed in rats at 4000 mg/kg/day of CPZ for a month, and was also depressed in rats at 4000, 2000, 1000 and 500 mg/kg/day of CPZ for six months.
3) Increase in urine volume and excretion of Na into urine were found at the termination of the dosing period in male and female rats receiving 4000mg/kg/day of CPZ for six months.
4) Dose-related enlargement of the lumen of the cecum was observed in male and female rats treated with CPZ or CET. In addition rats receiving the higher doses of CPZ or CET had the symptom of peritonitis, such as hyperemia of the peritoneum, ascites, perihepatitis, perisplenitis, peripancreatitis and so on in both subacute and chronic toxicities.
5) Hyaline droplet degeneration in the proximal tubular epithelium was observed in rats receiving up to 1000 mg/kg/day of CPZ. This change was tended to be recovered in rats of recovery test.
6) Thus, the no effect intraperitoneal dose level of CPZ in rats was thought to be 500 mg/kg/day from the present experiment.
