STUDIES ON THE PHARMACODYNAMICS AND PHARMACOKINETICS OF PACLITAXEL(Zisu ®)

Pharmacological studies demonstrated that paclitaxel (Zisu®) was very active in the inhibition of the growth of human cancer cell panel including KB cells, HCT-8, A2780, and MCF-7 cells. The IC₅₀ was as low as 0.0019, 0.0019, 0.0036 and 0.01 μg/ml respectively. Experimental therapeutic studies indicated that paclitaxel(Zisu®) significantly inhibited the growth of melanoma B-16, Walker carcinomsarcoma and heterotransplanted human ovarian cancer in nude mice. Biochemical pharmacological studies showed that paclitaxel (Zisu®) could accelerate microtubule assembly and inhibit its deassembly; population in G1 was decreased while the cell population in G2+M phase was increased significantly. In addition, a polyploid cell population appeared. Pharmacokinetic studies demonstrated that the t_l/2α was 0.12 h and t_l/2β was 5.02 h when it was injected intravenously at a dose of 5 mg/kg in rats. The AUC, Vc and CLs were 11.82(μg.h)/ml, 0.50L/kg and 0.42L(h.kg) respectively.