卡纳琳-紫杉醇混悬剂的制备及其腹腔化疗的药代动力学研究  

Preparation of carbon nanoparticle paclitaxel suspension and pharmacokinetic study of intraperitoneal chemotherapy

作　　者：蔡元坤 张兴源 

机构地区：[1]上海市第五人民医院普通外科,200125

出　　处：《中华胃肠外科杂志》2011年第12期973-976,共4页Chinese Journal of Gastrointestinal Surgery

摘　　要：目的制备卡纳琳．紫杉醇混悬剂并研究其腹腔化疗的药代动力学。方法高效液相色谱法测定卡纳琳-紫杉醇的饱和吸附率。制备混悬剂。将34只Wistar大鼠随机分为实验组与对照组．分别腹腔注射卡纳琳-紫杉醇混悬液及单纯紫杉醇溶液．给药后7d内的不同时间点取各组大鼠血液、肠系膜淋巴结及腹腔洗液样本．采用高效液相-二级质谱联用法对紫杉醇浓度进行分析。结果每1ml卡纳琳可饱和吸附7mg紫杉醇。实验组血浆药物曲线下面积（AUC）为对照组的0．63倍；淋巴结药物AUC为对照组的0．73倍；腹水药物AUC为对照组的1．25倍。实验组血浆药物代谢半衰期（tm）为对照组的1．61倍；腹水药物t^1/2为对照组的0．88倍；淋巴结药物t^1/2为对照组的1．10倍。结论卡纳琳对紫杉醇吸附作用良好。以卡纳琳-紫杉醇混悬剂行腹腔化疗具有血药浓度低、腹腔药物浓度高、安全性高的特点，但淋巴靶向性及淋巴组织滞留作用不明显，其机制有待进一步研究。Objective To prepare carbon nanoparticle-paclitaxel suspension （CNPS） and to study the pharmacokinetics of intraperitoneal chemotherapy with CNPS. Methods Saturated absorption capacity of carbon nanoparticle suspension （CNS） and paclitaxel were detected by high performance liquid chromatography in order to prepare the above suspension. Wistar rats were randomly divided into the experimental group （A） and the control group （B）, to which intraperitoneal injections of CNPS and paclitaxel were given respectively. At different time points, measure the blood samples, mesenteric lymph nodes, and intraperitoneal lavage fluid were collected to measure the concentration of paclitaxel. Results One ml CNS could absorb 7 mg paclitaxel by maximum. The ratio of area under the curve （AUC） in the plasma of group A to group B was 0.63. The ratio of AUC in lymph nodes of group A to group B was 0.75 and that in intraperitoneal lavage fluid was 1.25. The metabolic half-life （t^1/2） of paclitaxel in the plasma of group A was 1.61 times as long as that of group B. The t^1/2 of paclitaxel in intraperitoneal lavage fluid of group A was 0.88 as long as that of Group B. The t^1/2 of paclitaxel in lymph nodes of group A was 1.10 as long as that of Group B. Conclusions CNS has a high absorption capacity with paclitaxel. Intraperitoneal chemotherapy by CNPS is characterized by low drug concentration in the blood, high drug concentration in the peritoneal cavity and high safety. However, the targeting and lymphatic retention effect are not significant. The mechanism warrants further investigation.

关 键 词：卡纳琳 卡纳琳-紫杉醇混悬剂 腹腔化疗 淋巴靶向化疗 药代动力学 

分 类 号：R965[医药卫生—药理学]