Sci. Pharm. 2010; 78: 445–450
Absorption, Distribution and Excretion of 14C-Probimane in Mice Bearing Lewis Lung Carcinoma
Da-Yong LU * 1,2, Rui-Ting CHEN 2, Ting-Ren LU 3, Hong-Ying WU 3, Rong-Xin QU 1, Jin-Yu CHE 1, Bin XU 2
1 Shanghai University, Shanghai 200444, PR China.
2 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
3 College of Science, Shanghai University, Shanghai 200444, PR China.
* Corresponding author. E-mail: email@example.com (D.-Y. Lu)
Spontaneous neoplasm metastasis, a fatalist pathological feature of cancer, is a long-evolving, multi-steps process that can now only be treated or controlled by drugs or immuno-modulators. Probimane (Pro), as a representative of the wellknown class of antimetastatic agents 'Bisdioxopiperazine compounds (Biz)', is systematically studied for its absorption, distribution and excretion in mice bearing Lewis lung carcinoma by a radioactivity-detective method in this investigation. It is found that the 14C-Pro concentrations in different normal organs of mice at 2 hrs are very high and dramatically declined at 24 and 48 hrs. However, Pro concentrations in metastatic foci are slightly changed at the same time. Almost no change of Pro concentrations is observed in pulmonary metastatic nodules within 48 hrs. This evidence can be used to explain the characteristics of good metastatic inhibition by Biz compounds. The radioactivity in brain is relatively low because Pro can hardly penetrate into the blood-brainbarrier to eliminate brain tumors. The excretion of 14C-Pro is observed at the same ratios from both urine and feces and also at constant rates. These data are much useful for better understanding of the general pharmacological characters and possible antimetastatic mechanisms of actions of probimane and other Biz compounds from a new perspective and research angles.
Anti-cancer agents • Bisdioxopiperazine compounds • Cancer chemotherapy • Probimane • Drug distribution
Received May 12th, 2010 | Accepted June 15th, 2010 | Published Online June 15th, 2010