中国中药杂志

2005, (20)

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羟基喜树碱腹腔内给药的药代动力学研究
Pharmacokinetic study of intraperitoneal chemotherapy with HCPT

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)

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

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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)

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