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  • Title: [Subacute toxicity test of cefoperazone in beagle dogs with the intravenous administration for 3 months (author's transl)].
    Author: Yoneda T, Masatani H, Shibata T, Kawamura Y, Sato S, Iwasaki S, Takimoto Y, Nagasawa M, Takai A.
    Journal: Jpn J Antibiot; 1980 Oct; 33(10):1028-55. PubMed ID: 6451720.
    Abstract:
    The subacute toxicity test of cefoperazone (CPZ) in Beagle dogs with the intravenous administration for 35 days has been reported from our laboratory. In the present experiments, the subacute toxicity test of CPZ in Beagle dogs was carried out for longer administration period than before. CPZ was given intravenously to each group (2 or 4 dogs) at dose level of 100 mg/kg/day, 200 mg/kg/day and 400 mg/kg/day respectively for 3 months. Cefazolin (CEZ) was used intravenously for positive control using 4 dogs at dose level of 200 mg/kg/day and physiological saline was given intravenously to 2 dogs for 3 months. 1) In Beagle dogs received high dose of CPZ, transient vomiting, salivation and diarrhea were observed immediately after the administration. 2) Signs of anemia, such as decrease of erythrocyte and value of hemoglobin and hematocrit, and increase of reticulocytes of the peripheral blood and in fragility of red cell associated with decrease of food intake, were observed in 2 female dogs given CPZ of 400 mg/kg/day. In only one of these dogs, a positive reaction of COOMBS' test was shown. The anemia recognized in these 2 dogs seems to be of hemolytic nature. 3) The weight of thymus was decreased in all of 4 dogs given CPZ at 400 mg/kg/day and in 2 out of 4 dogs given CPZ at 200 mg/kg/day, respectively. 4) Based on the fact that no abnormalities were found in dogs given CPZ at 200 mg/kg/day except a slight decrease of weight of thymus in some of them, the maximum safety dose of CPZ was thought to be 200 mg/kg/day.
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