活性炭吸附丝裂霉素C腹腔化疗的药代动力学研究

目的探讨活性炭吸附丝裂霉素C（MMC—CH）腹腔化疗的药代动力学特征。方法建立人胃癌裸鼠模型,分别采取静脉注射MMC、腹腔注射水剂MMC及腹腔注射MMC—CH的给药方式,于给药后不同时间点,采用高效液相色谱法测定淋巴结、大网膜、血浆及腹腔液的MMC浓度,分析不同给药方法的药物代谢动力学特征。结果MMC—CH腹腔化疗可以在腹腔液、大网膜和淋巴结形成高药物浓度,并可维持24h以上,血浆药物浓度低。水剂MMC腹腔化疗可以形成短暂的腹腔液高药物浓度,但足不能在血浆、大网膜及淋巴结中形成高药物浓度。静脉MMC化疗可以在大网膜内形成短暂的高药物浓度,但是腹腔液和淋巴结药物浓度低,血浆药物浓度高。结论MMC—CH腹腔化疗可以在腹腔液、大网膜和淋巴结内形成持续24h以上的高药物浓度,同时血药浓度非常低。MMC—CH腹腔化疗是一种有效的辅助治疗方法,并可以达到淋巴化疗目的。

Pharmacokinetic study of intraperitoneal chemotherapy with mitomycin C bound to activated carbon particles

Objective To analyze the pharmacokinetics of intraperitoneal chemotherapy with mitomycin C (MMC) bound to activated carbon particles. Methods A nude mouse model with transplanted human gastric cancer was established. The mice were given MMC by i.v. or intraperitoneal (i.p.) injections, or given i.p. MMC bound to activated carbon particles (MMC-CH) . Pharmacokinetic assays were carried out at different time points (0.5,1,2,3,6,12 and 24 h) in 7 mice per each time point, to compare the MMC concentrations revealed by the above mentioned methods. Results The MMC concentration in peritoneal exudate, omentum and lymph nodes of MMC-CH group was significantly higher than that of MMC solution i.p. group and MMC i.v. group (P<0.001). On the other hand, the MMC level in serum was significantly lower than that in two control groups (P<0.001). High MMC level was maintained longer than 24 hours in the MMC-CH group. Intraperitoneal chemotherapy with MMC solution resulted in a low MMC concentration in serum,peritoneal exudates and lymph nodes,and only a transient high level of MMC in the omentum. After i.v. administration, a significantly higher level of MMC concentration occurred in the serum, but only a shortly increased concentration of MMC in the omentum, and lower concentration in peritoneal exudate and lymph nodes as compared with those in the other two groups (P<0.001). Conclusion High concentration of MMC in peritoneal exudate, omentum and lymph nodes maintained longer than 24 hours and a significantly lower MMC serum concentration can be achieved by administration of intraperitoneal administration of MMC bound to activated carbon particles.