Science Links Japan | A Repeated Dose Toxicity Study of Amrubicin Hydrochloride(SM-5887) Administered Intravesically to Beagle Dogs for 2 Weeks Followed by a 3 Week Recovery Period.

A Repeated Dose Toxicity Study of Amrubicin Hydrochloride(SM-5887) Administered Intravesically to Beagle Dogs for 2 Weeks Followed by a 3 Week Recovery Period.

Accession number;99A0241089

Title;A Repeated Dose Toxicity Study of Amrubicin Hydrochloride(SM-5887) Administered Intravesically to Beagle Dogs for 2 Weeks Followed by a 3 Week Recovery Period.

Author; SAMESHIMA HIDENOBU (Shin Nippon Biomedical Lab., Ltd.) OKASAKI KEIKO (Shin Nippon Biomedical Lab., Ltd.) ONIMARU TOSHIO (Shin Nippon Biomedical Lab., Ltd.) SATO KEN'ICHI (Shin Nippon Biomedical Lab., Ltd.) NAGATA RYOICHI (Shin Nippon Biomedical Lab., Ltd.)

Journal Title;Japanese Pharmacology & Therapeutics

Journal Code:Z0947A

ISSN:0386-3603

VOL.27;NO.Suppl.1;PAGE.S.245-S.306(1999)

Figure&Table&Reference;FIG.4, TBL.12, REF.3

Pub. Country;Japan

Language;Japanese

Abstract;Amrubicin Hydrochloride(SM-5887) was administered intravesically to 3 female Beagle dogs at dose levels of 0(control), 0.6, 2.0 and 6.0mg/kg for 2 weeks, in order to evaluate its toxicity. Additional 2 females were included in the control and high dose groups to assess the reversibility of any changes. In the 6.0mg/kg group, 2 animals died, 1 on the final day of the dosing period and the other on Day 3 of the recovery period. One animal was sacrificed on Day 6 of the recovery period. A decrease in spontaneous activity, sedation, hypothermia, lateral position or pale mucosa were observed in these animals. Additionally, decreases in body weight because of loss of appetite or decrease in food consumption and decrease in water consumption were noted. In the surviving animals of the 6.0mg/kg group, decreases in food consumption, water consumption and body weight in all animals, and a decrease in spontaneous activity in 1 animal were observed. Decrease in food consumption and body weight were also noted in 2 animals of the 0.6mg/kg group and in 1 animal of the 2.0mg/kg group. Red urine was observed in the control group early in the dosing period, and in the test article groups throughout the dosing period. Similarly in the 6.0mg/kg group, red urine was observed up until the time of death during the recovery period. In urinalysis, high positive occult blood reaction, high protein(>300mg/dl) and a high incidence of erythrocytes in urine sediment were frequently observed in any dosing group. In the 6.0mg/kg group at Week 2 of the dosing period, a high leukocyte count(mainly increases in neutrophil and monocyte counts) was noted in hematology. In serum biochemistry, high or a tendency towards high values in BUN, creatinine, uric acid, phospholipid and globulin ratio were noted. Additionally, low or a tendency towards low values in Na,Cl, albumin ratio and A/G ratio were noted in the 6.0mg/kg group.... (author abst.)

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