Hematotoxicity and Vascular Irritation of DA-125, A New Anthracycline Anticancer Agent

새로운 Anthracycline 항암제 DA-125의 조혈기독성 및 혈관장해성

Hematotoxicity and vascular irritation of DA-125, a new anthracycline antitumor antibiotic, were investigated in mice and rabbits. In hematotoxicity study, healthy male ICR mice were treated with DA-125 by a single intravenous injection at doses of 18 and 24 mg/kg. After 4, 8, 12 and 16 days WBC count, RBC count, hemoglobin concentration, hematocrit value, and platelet counts were measured respectively. As a positive control, 12 mg/kg of doxorubicin (DXR) was used in the same manner. Remakable reductions of WBC counts in groups treated with DA-125 or DXR were observed 4 days after administration and returned to normal range 8 days after injection in groups of DA-125 18 mg/kg and DXR 12 mg/kg. The recovery of leukopenia induced in a group of DA-125 24 mg/kg took about 16 days after administration. The RBC counts, hemoglobin concentrations and hematocrit values also decreased in all drug treated groups on day 8 and recovered thereafter. The platelet counts of groups treated with DA-125 or DXR decreased on day 4 and recovered from day 8 of experiment. Local vascular irritation of DA-125 was also assessed in rabbits. The obtained results can be summarized as follows. 1. Thrombophlebitis was not induced even after daily intravenous administration of 0.4% solution of DA-125 or 0.2% solution of DXR for 7 days. 2. Macro- and microscopic observations revealed that the irritative activity of 0.4% solution of DA-125 in blood vessels was not so much different from that of saline when they were injected once a day into vein retroauricularis of rabbits for 7 days. 3. Mild inflammatory reaction was noted around vessels in rabbits treated with 0.2% solution of DXR after consecutive intravenous infusion for more than 5 days. 4. The potencies of vascular irritation of the test solutions were summarized in the following order; saline = 0.4% DA-125<0.2% DXR. These results indicated that DA-125 showed similar pattern of hematotoxicity with DXR but was less hematotoxic than DXR, and that 0.4% solution of DA-125 did not elicit unusual toxic properties when injected through intravenous route for clinical practice.