Six-month Intravenous Toxicity Study of Amrubicin Hydrochloride(SM-5887) in Beagle Dogs followed by 6-month Recovery Study.
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Accession number;99A0241091
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| Title;Six-month Intravenous Toxicity Study of Amrubicin Hydrochloride(SM-5887) in Beagle Dogs followed by 6-month Recovery Study. |
| Author;
SHIGENO HITOSHI
(Saf. Res. Inst. for Chem. Compd. Co. Ltd.)
ICHINOHE HITOSHI
(Saf. Res. Inst. for Chem. Compd. Co. Ltd.)
FURUKAWA MASATOSHI
(Saf. Res. Inst. for Chem. Compd. 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.333-S.419,S.421(1999)
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| Figure&Table&Reference;FIG.9, TBL.24, REF.9 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Amrubicin hydrochloride(SM-5887), anthracycline antitumor antibiotic, was investigated for its intravenous toxicity by intravenous administration in beagle dogs for 6 months, followed by 6-month recovery study. Although the studying doses were set at 0.01, 0.07 and 0.5mg/kg/day at first, 3/6 of the males in the 0.5mg/kg/day group died or were sacrificed because of moribundity at the early stage of administration. Consequently, the high dose was changed to 0.3mg/kg/day(on day 10 or 11 of administration in males, on day 3 or 4 of administration in females), and three additional males were applied to this group. Six-month intravenous administration of SM-5887 in beagle dogs resulted in the following effects: Spermatogenetic disorder in males of the 0.07 and 0.3mg/kg groups; injury at the injection sites(cephalic vein) in males and females of the 0.07 and 0.3mg/kg groups; loss of hair, suppression of hematopoietic system, mainly of erythrocytic series, and lesion in the epithelium of pyloric gastric pits in males and females of the 0.3mg/kg group. As a result of 6-month withdrawal of SM-5587-treatment, the spermatogenetic disorder in males of the 0.3mg/kg group at the end of recovery period was observed in the same grade as that at the end of administration period, but regenerations of the spermatogonia, spermatocytes, and spermatidis were observed in a part of tubules; therefore, this disorder was considered to have partly recovered. Injury at the injection sites(cephalic vein) in males and females of the 0.07 and 0.3mg/kg groups subsided, and all of the other changes recovered. On the basis of these results, non-observed-effect level was estimated to be 0.01mg/kg/day for males and females in the present study. (author abst.) |
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