The Pharmacokinetic Study Of 10-propionyloxy Camptothecin In Rat Plasma

Camptothecin is a natural alkaloid isolated from Camptotheca acuminata,which has been widespread concerned due to its strong anti-tumor activity.10-propionyloxy camptothecin are bioactive derivatives of camptothecin.In the present study,the antitumor activity of 10-propionyloxy camptothecin and 10-hydroxy camptothecin was tested in vitro against two different cancer cells.Further the pharmacokinetic studies of 10-propionyloxy camptothecin and its metabolite 10-Hydroxy camptothecin were demonstrated in rat.To elucidate the potential activity of 10-propionyloxy camptothecin and 10-Hydroxy camptothecin,we tested their antitumor activity against two cancer cell lines,2774(human ovarian cancer cell line)and HT29(human colon cancer cell line),which is compared with camptothecin and 10-hydroxycamptothecin.The results showed that,compared with 10-hydroxy camptothecin,the in vitro antitumor activity of 10-propionyloxy camptothecin was significantly potent.10-hydroxy camptothecin was identified as the major metabolite of 10-propionyloxy camptothecin in rat microsome by HPLC/photodiode array detection(PDA)and LC-MS/MS analysis.An HPLC method coupled with fluoresce detection was developed to quantitatively determine 10-propionyloxy camptothecin and 10-hydroxy camptothecin in rat plasma.The method was simple,quickly,accurate and precise,selectivity enough and has been successfully applied to the pharmacokinetic study.The pharmacokinetic study of 10-propionyloxy camptothecin and its metabolite 10-Hydroxy camptothecin in rat plasma was investigated after after intravenous(i.v.)administration at a dose of 5 mg·kg-1.The results showed that,after i.v.administration,the level of 10-propionyloxy camptothecin and 10-hydroxy camptothecin reached the maximum concentration immediately.But 10-propionyloxy camptothecin concentration was significantly lower than HCPT and rapid declined to undetectable after 4h.AUC0-24 and AUC0-∞.of 10-propionyloxy camptothecin were 12.54±2.75 h·ng·mL-1和 3.69±4.44 h·ng·mL-1,about 1%of that of 10-hydroxy camptothecin which were 306.42±188.63 h·ng·mL-1和311.16±188.81 h·ng·mL-1 respectively.