Four-week Intravenous Toxicity Study of Amrubicin Hydrochloride(SM-5887) in Dogs.
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Accession number;99A0241087
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| Title;Four-week 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.)
ITO SEIICHI
(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.111-S.219(1999)
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| Figure&Table&Reference;FIG.18, TBL.13, REF.6 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Amrubicin hydrochloride(SM-5887), anthracycline antitumor antibiotic, was investigated for its toxicity by repeated intravenous administration in beagle dogs at the doses of 0.08, 0.15, 0.3 and 0.6mg/kg/day for 4 weeks, followed by 4-week recovery study to examine the reversibility of the treatment related effects. To compare the findings with SM-5887, 0.3mg/kg/day of doxorubicin was administered in the same manner. During four-week administration of SM-5887, clinical signs, i.e. frequent incidences of loose feces, mucous feces and/or diarrhea, and sporadic incidences of mucous bloody feces and bloody feces, in the animals receiving 0.6mg/kg were observed. Food consumption and body weight were decreased in the 0.6mg/kg group. In clinical pathology, obviously decreased leukocyte count and platelet count, slight reduction of erythrocyte count, hemoglobin concentration and hematocrit value, and suppression of myeloid cell were noted in the 0.6mg/kg group. Remarkable decreases in thymus and testes weights were observed in the 0.3 and 0.6mg/kg groups. In microscopic examination, atrophy of seminiferous tubules, degeneration and hypoplasia of ovaries were observed in the 0.15, 0.3 and 0.6mg/kg groups. Disorders in the stomach, atrophy of the spleen, thymus and lymph node were observed in females of the 0.3mg/kg and in both sexes of the 0.6mg/kg groups. Suppression of the hematopoietic system and disorders in the small intestine were also observed in the 0.6mg/kg group. Accordingly, intravenous administration of SM-5887 produced toxicological effects in digestive, hematopoietic, lymphatic, and reproductive systems. On the other hand, doxorubicin resulted in the same toxic signs as SM-5887, thought doxorubicin is at least twice as potent as SM-5887 by comparison with each toxic dosage level. As a result of 4-week withdrawal of SM-5887 treatment, all of the changes recovered except for decreased testes weight and atrophy of the seminiferous tubules.... (author abst.) |
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