Five-day Intravenous Comparative Toxicity Study on Amrubicin Hydrochloride(SM-5887) and Doxorubicin Hydrochloride(DXR) in Male Rats.
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Accession number;99A0241088
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| Title;Five-day Intravenous Comparative Toxicity Study on Amrubicin Hydrochloride(SM-5887) and Doxorubicin Hydrochloride(DXR) in Male Rats. |
| Author;
ADACHI HARUHIKO
(Sumitomo Chemical Co., Ltd.)
NAKAYAMA ATSUMI
(Sumitomo Chemical Co., Ltd.)
HORII KAZUNARI
(Sumitomo Chemical Co., Ltd.)
OZAKI MASAKAZU
(Sumitomo Chemical Co., Ltd.)
UWAGAWA SATOSHI
(Sumitomo Chemical Co., Ltd.)
SEKI TAKAKI
(Sumitomo Chemical Co., Ltd.)
MATSUO MASATOSHI
(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.221-S.244(1999)
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| Figure&Table&Reference;FIG.25, TBL.8, REF.9 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;A five-day intravenous comparative toxicity study on Amrubicin Hydrochloride(SM-5887) and Doxorubicin Hydrochloride(DXR) was conducted in Sprague-Dawley male rats at dosages of 2 and 4mg/kg/day of SM-5887, and 2mg/kg/day of DXR. The following treatment-related changes were detected in this study. At the end of the treatment period, increased incidences of atypia of gastro-intestinal mucosal cells and hypocellularity of bone marrow, decreased spleen and thymus weights, decreased lymphocyte counts, increased incidences of loss of hair and atrophy of hair follicles were observed in animals given 2 and 4mg/kg of SM-5887, and in animals given DXR. Moreover, the following changes due to poor conditions were observed in animals given SM-5887 and DXR; decreases of liver or prostate weights, significant changes in plasma urea nitrogen, total cholesterol, phospholipid, glutamic oxalacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, calcium and/or albumin/globulin ratio. At the early stage of the withdrawal period, 4 animals given 4mg/kg of SM-5887 and one animal given DXR were found dead or killed in extermis. Factors contributory to death for these animals were considered to be dysfunction of the digestive system or hematopoietic system. At the latter half of the withdrawal period, 3 animals given DXR were found dead or killed in extermis. Factors contributory to death for these animals were considered to be dysfunction of the cardiovascular system, because increases in plasma lactate dehydrogenase and creatine phosphokinase, increased incidences of organized thrombus in atrial auricles, and myocardial vacuolation were observed in these animals. At the end of the withdrawal period, increased incidences of small testes and atrophy of seminiferous tubules were observed in animals given SM-5887.... (author abst.) |
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