Single Intravenous Toxicity Study of Amrubicin Hydrochloride(SM-5887) in Dogs.
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Accession number;99A0241084
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| Title;Single Intravenous Toxicity Study of Amrubicin Hydrochloride(SM-5887) in Dogs. |
| Author;
KODA AKIRA
(Sumitomo Chemical Co., Ltd.)
NODA TOMOHIRO
(Sumitomo Chemical Co., Ltd.)
HORII KAZUNARI
(Sumitomo Chemical Co., Ltd.)
INOUE KAORU
(Sumitomo Chemical Co., Ltd.)
OZAKI MASAKAZU
(Sumitomo Chemical Co., Ltd.)
KATO TERUSHIGE
(Sumitomo Chemical Co., Ltd.)
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Journal Title;Japanese Pharmacology & Therapeutics
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Journal Code:Z0947A
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ISSN:0386-3603
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VOL.27;NO.Suppl.1;PAGE.S.37-S.62(1999)
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| Figure&Table&Reference;FIG.10, TBL.12, REF.6 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Amrubicin hydrochloride(SM-5887), anthracycline antitumor antibiotic, was investigated for its toxicity by single intravenous administration in beagle dogs at the doses of 1,2,3,4 and 6mg/kg. To compare the findings with SM-5887, 1,2 and 4mg/kg of doxorubicin was administered in the same manner. A single-dose administration of SM-5887 resulted in the following toxic signs: Three or four days after treatment, each one of two animals receiving 4 or 6mg/kg was found dead. Clinical signs, i.e. emesis, loose feces and mucous feces in all treated groups, diarrhea at 2mg/kg and higher, and bloody feces and decrease of spontaneous activity in the 4 and 6mg/kg groups, were observed. Food consumption was decreased at 2mg/kg and higher dosages. Body weight was reduced at 3mg/kg and higher dosages. In clinical pathology, decreased leukocyte count at 4 and 6mg/kg, decreased platelet count at 2mg/kg and higher dosages, and elevation of GPT, GOT and ALP in the surviving animals receiving 6mg/kg were noted. In histopathology, dead animals receiving 4 or 6mg/kg showed disorder of intestinal mucosa and severe suppression of hematopoietic system. In surviving animals, examination of intestine only demonstrated dilated crypt at 3 and 6mg/kg, suggesting quick recovery from the effects of treatment. In addition, spermatogenetic disorder in males of the 3 and 6mg/kg groups, hyperplasia of granulocyte in bone marrow in the 6mg/kg group, and slight increase in M/E ratio in the 4mg/kg group were observed. On the other hand, two animals receiving 4mg/kg of doxorubicin died four or five days after treatment. Doxorubicin resulted in the same toxic signs as SM-5887, though doxorubicin is at least two or three-fold as potent as SM-5887 by comparison with each toxic dosage level. (author abst.) |
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