Study On The Tissue Distribution Of 10-propionyloxy Camptothecin In Rats

Camptothecin(CPT)is a naturally occurring alkaloid first isolated from the native Chinese tree Camptotheca acuminata Dence.(Nyssaceae)in 1966.CPT has been paid considerable attention because of its significant anti-tumor activity.HCPT(10-hydroxycamptothecin),clinically used in China,is a natural bioactive derivative of camptothecin and has been confirmed to possess high anti-cancer properties.10-propionyloxy camptothecin(PCPT)is esterified in the 10-hydroxyl position from HCPT.In the present study,the in vivo antitumor activity of PCPT against mouse Lewis Lung cancer was tested through the transplanted tumor C57BL/6J mouse model.Furthermore,the tissue distribution studies of PCPT and its metabolite HCPT were elucidated.Cottonseed oil as the dispersant,the in vivo anti-cancer activity of PCPT were investigated by intragastric administration at different doses(1 mg/kg,0.5mg/kg,and 0.1mg/kg)against Lewis lung cancer in mice transplanted tumor model.After 17 days of treatment,the body weight among different groups showed no significant difference.The inhibition rate reached 78?88%,displaying the significant in vivo antitumor effect of PCPT.A sensitive and reliable RP-HPLC method coupled with fluorescence detection was developed and validated for the simultaneous analysis of PCPT and HCPT in rat tissue samples.The tissue distribution of PCPT and its metabolite HCPT were determined for rats after each receiving a single i.v.dose of 5 mg/kg PCPT via the tail vein.The results indicated that the content of PCPT was the highest in lung,then in liver and spleen and lowest in brain and heart,while the content of HCPT was higher in lung and liver than in other tissues.