叶孟,林晓霞,潘宏铭,李楠,楼芳,金伟,郑宇,吴金民
YE Meng,LIN Xiao-xia,PAN Hong-ming,LI Nan,LOU Fang,JIN Wei,ZHENG Yu,WU Jing-min(Oncology center,Sir Run Run Shaw Hospital,Zhejiang University,Hangzhou 310016,China)

• 1:浙江大学附属邵逸夫医院
• 2:浙江大学附属邵逸夫医院
• 3:浙江大学附属邵逸夫医院
• 4:浙江大学附属邵逸夫医院

摘要(Abstract)：

目的:研究羟基喜树碱(HCPT)腹腔内给药的药代动力学特点。方法:比格犬6只,HCPT剂量2 mg.kg-1,溶于50 mL生理盐水中,先腹腔内注入250 mL生理盐水,随后用恒速泵快速注入HCPT;随后按不同时间点抽取血液和腹腔液,各样本用高效液相色谱分析药物浓度,并用3p87软件包计算药代动力学参数。结果:腹腔液HCPT的AUC与外周静脉血及门静脉血AUC之间的比值分别为45∶1和37∶1,P值均小于0.001;腹腔液HCPT浓度明显高于外周静脉给药组的腹腔液浓度,峰值为60.4倍,AUC为21倍。P值均小于0.001。结论:腹腔内给药其药代动力学具有明显优越性,能维持腹腔液和门静脉血更高更持久的血药浓度,因而有利于化疗药物发挥更大的生物学效应,值得临床应用。
Objective: To study the pharmacokinetic of 10-Hydroxycamptothecin HCPT by intraperitoneal administration.Method: Six dogs were given HCPT by intraperitoneal perfusion: HCPT 2 mg·kg^(-1),dissolved in 300 mL NS.During the course of experiments,peritoneal fluids and blood were sampled using a standardized protocol.The concentration of HCPT in all samples was determined by high performance liquid chromatography(HPLC).Result: The area under the curve(AUC) of peritoneal fluids was significantly highly as compared to the AUC of femoral vein and portal vein(P<0.001).Conclusion: These experiments demonstrate that intraperitoneal chemotherapy has significant effect on the pharmacokinetics of IP route of HCPT administration.This method should be a more reasonable chemotherapy for the prevention of recurrence and liver metastasis of gastric cancer,colon cancer and ovary cancer after radical resection.

关键词(KeyWords)： 羟基喜树碱;药代动力学;腹腔内化疗;色谱法
10-hydroxycamptothecin;pharmacokinetic;intraperitoneal chemotherapy;chromatography

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 叶孟,林晓霞,潘宏铭,李楠,楼芳,金伟,郑宇,吴金民
YE Meng,LIN Xiao-xia,PAN Hong-ming,LI Nan,LOU Fang,JIN Wei,ZHENG Yu,WU Jing-min(Oncology center,Sir Run Run Shaw Hospital,Zhejiang University,Hangzhou 310016,China)

参考文献(References)：

• [1]Ajani J A,Baker J,Pisters P W,et al.CPT-11 plus cisplatin in pa-tients with advanced,untreated gastric or gastroesophageal junctioncarcinoma:results of a phaseⅡstudy.Cancer,2002,94(3):641.
• [2]Ribrag V,Koscielny S,Vantelon J M,et al.PhaseⅡtrial ofirinotecan(CPT-11)in relapsed or refractory non-Hodgkin’s lym-phomas.Leuk Lymphoma,2003,44(9):1529.
• [3]刘健,胥彬.羟基喜树碱内药物在癌症联合化疗应用中的新进展.肿瘤,1998,4:302.
• [4]Zhang R,Li Y,Cai Q,et al.Preclinical pharmacology of the natu-ral product anticancer agent 10-hydroxycamptothecin,an inhibitor oftopoisomerase.Cancer Chemother Pharmacol,1998,41:257.
• [5]张力,李苏,廖海,等.羟基喜树碱Ⅰ期药代动力学及人体耐受性临床研究.癌症.2001,20(12):1391.
• [6]Gil-Delgado M A,Guinet F,Castaing D,et al.Prospective phaseⅡtrial of iriontecan,5-fluorouracil,and leucovorin in combinationas salvage therapy for advanced colorectal cancer.Am J Clin Oncol,2001,24(1):101.
• [7]Louvet C,Andre T,Gamelin E,et al.A phaseⅠ-Ⅱ,dose-esca-lating trial of ZD9331 in combination with irinotecan(CPT11)in pre-viously pretreated metastatic colorectal cancer patients.Bull Cancer,2004,91(12):279.
• [8]刘健.羟基喜树碱类药物作用机制及合并治疗中机理的研究.中国肿瘤临床,1998,25(5):389.
• [9]Witkamp A J,Bree E D,Goethem A R V,et al.Rationale andtechniques of intra-operative hyperthermic intraperitoneal chemothera-py.Cancer Treat Rev,2001,27(6):365.
• [10]Glehen O,Mithieux F,Osinsky D,et al.Surgery combined withperitonectomy procedures and intraperitoneal chemohyperthermia inabdominal cancers with peritoneal carcinomatosis:a phaseⅡstudy.J Clin Oncol,2003,21(5):799.
• [11]Yano M,Yasuda T,Fujiwara Y,et al.Preoperative intraperitonealchemotherapy for patients with serosa-infiltrating gastric cancer.JSurg Oncol,2004,88(1):39.
• [12]Yonemura Y,Endou Y,Bando E,et al.Effect of intraperitoneal ad-ministration of docetaxel on peritoneal dissemination of gastric cancer.Cancer Lett,2004,210(2):189.