ACTION OF 7-ETHYLCAMPTOTHECIN ON TUMOR-CELLS AND ITS DISPOSITION IN MICE

  • 1 April 1987
    • journal article
    • research article
    • Vol. 71 (4), 341-348
Abstract
Some biological effects of camptothecin (CPT) and its new derivative 7-ethylcamptothecin (ECPT) were studied. The drugs were effective against murine leukemia; ECPT was more effective than CPT. Ip administration of ECPT or CPT gave maximum treated/control values of 325% and 232%, respectively. The drugs also inhibited the growth of KB cells in vitro, 50% effective doses of 3.5 ng/ml of ECPT and 8.6 ng/ml of CPT, indicating the stronger activity of ECPT. Pharmacokinetic studies of the drugs in mice showed that ECPT had a longer biological half-life in the terminal phase and a larger amount remained in the plasma compared with CPT. After iv administration of ECPT, the drug accumulated in the intestine, suggesting that the main route of excretion of the drug is through the biliary tract. The study on cell cycle progression by flow cytometry suggested that the main effect of both drugs on L1210 cells was the blocking of G2-M phase. These results suggest that the main reasons for the superior antitumor activity of ECPT compared with CPT are as follows: (a) ECPT had a stronger growth-inhibiting activity against tumor cells, and (b) ECPT remained in the intestinal tract for a longer time and in higher amounts when administered in vivo.