Teratogenicity Study of SKI 2053R, a New Platinum Anticancer Agent, in Rabbits

새로운 백금착물 항암제 SKI 2053R의 토끼 최기형성시험

SKI 2053 R, cis-Malonato [(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II), is a newly developed antitumor platinum complex derived from cisplatin. Preclinical studies suggest that it may have greater antitumor activity and lower toxicity than cisplatin. Effects of test agent on general toxicity of does and embryonic development of Fl fetuses were investigated in rabbits. Sixty eight New Zealand white rabbits were distributed among three treated groups and a control group. SKI 2053R was administered intravenously to pregnant rabbits from days 6 to 18 of gestation at dose levels of 0, 0.67, 2.0, or 6.0 mg/kg/day. The pregnant does were subjected to the caesarean section on day 28 of gestation. No treatment-related changes in clinical signs, body weight, food consumption, and necropsy findings were observed in all groups. Fl fetuses showed no changes related to the treatment of SKI 2053R, except that an increase in the incidence of skeletal variations were observed at 6.0 mg/kg. There were no signs of material toxicity or embryotoxicity at 0.67 and 2.0 mg/kg. The results show that the administration of 6.0 mg/kg SKI 2053R induces skeletal variations in fetuses and that the no observed adverse effect levels(NOAELS) of SKI 2053R are considered to be over 6.0 mg/kg for does and 2.0 mg/kg for Fl fetuses in rabbits.