结肠旁植入氟尿嘧啶缓释剂化疗的药代动力学实验研究

Experimental Study on Pharmacokinetics of Chemotherapy via Para-colon Approach Implanted with Sustained-Release Preparation 5-fluorouracail

[目的]探讨结肠旁植入氟尿嘧啶缓释剂化疗的药代动力学变化及其意义。[方法]健康成年杂种犬25只分为实验组(20只)和对照组(5只)。手术经腹乙状结肠旁单点植入氟尿嘧啶缓释剂(中人氟安)200mg,门静脉留置插管。按不同时段取距植药点不同距离的组织、不同站点的淋巴结以及外周、门静脉血样,HPLC法检测药物浓度。[结果]植药点局部组织和淋巴结药物浓度以植药点为中心随距离增加浓度递减;门静脉、局部组织及淋巴结的药物浓度随着植药时间的延长递减;植药后15天,距植药点15cm处组织浓度为0.101±0.015μg/g,肠系膜淋巴结浓度为0.204±0.059μg/g,门静脉内药物浓度0.102μg/ml,均大于抑瘤浓度(0.1μg/ml)。[结论]结肠旁植入氟尿嘧啶缓释剂化疗能使局部组织、淋巴结以及门静脉血持久维持较高的有效药物浓度,可作为预防和治疗结直肠癌术后局部复发和肝转移的一种有效的辅助化疗手段。

[PUrpose] To explore the pharmacokinetics and its significance of chemotherapy via pora-colon approach implanted with sustained-release preparation 5-fluorouracail. [Methods] Twenty-five adult hybrid dogs were divided into two groups（chemotherapy group,20 dogs; control group, 5 dogs）. Sustained-release preparation 5-fluorouracail（Zhong Ren Fu An, 200mg） was imbedded at one point in para-sigmoid colon via abdomen operation. A pipe was inserted into portal vein for collecting blood samples. At different time points, tissue samples in different distance from the imbed point and different lymphoid node and blood samples from periphery and portal vein were collected to be taken for drug concentration measurement in HPLC method. [Results] The drug concentration of local tis- sue and different lymphoid node decreased gradually at distance increase around the imbed point. The drug concentration of portal vein, local tissue and lymphoid node also decreased at time prolong. At 15 days point, drug concentration of tissue 15cm away from imbed point（0.101±0.015μg/g）,mesentery lymphoid node（0.204±0.0591μg/g） and portal vein（0.102μg/ml）were all more than treatment concentration（0.1μg/ml）. [Conclusions] The chemotherapy of via para-colon approach implanted with sustained-release preparation 5-fluorouracail may maintain lasting, effective and high concentration in tissue, lymphoid node and portal vein. It is an effective and secondary chemotherapy of prevention and treatment for local recurrence and live metastasis in postoperative patients with colon-rectum cancer.