论文部分内容阅读
目的:考察抗肿瘤新药乙烷硒啉在大鼠和结肠癌荷瘤裸鼠体内的组织分布规律。方法:采用荧光分光光度法和液相色谱-质谱联用法分别测定SD大鼠和人结肠癌LS174T细胞荷瘤裸鼠灌服乙烷硒啉后各组织中药物浓度经时变化。结果:大鼠灌服乙烷硒啉2 h后,药物广泛分布于各组织,以胃肠及其内容物、肝、肾中含量最高;24 h肝肾组织硒浓度分别为(6.14±0.87)和(6.93±0.94)μg.g-1,同时间点血液中硒浓度为(4.43±1.65)μg.mL-1;48 h后除肾脏外,其他各组织硒浓度数值均低于血硒浓度。结肠癌裸鼠给药后1 h即可见原形药迅速分布于各组织,至24 h肾脏药物浓度达峰值,而其他组织中药物浓度显著降低,至48 h肿瘤中仍可检测出较高药物浓度。结论:乙烷硒啉口服给药后在大鼠和结肠癌荷瘤裸鼠体内均可广泛分布,并对肿瘤组织具有一定选择性,其组织分布特点可能与药物的代谢排泄途径相关。
Objective: To investigate the tissue distribution of antineoplastic new ethaselen in rat and colon cancer-bearing nude mice. Methods: Fluorescence spectrophotometry and liquid chromatography-mass spectrometry (LC-MS / MS) were used to determine the concentration of ethaselen in nude mice bearing SD and LS174T human colon cancer cells. Results: The rats were orally administered with ethaneselen for 2 h. The drugs were widely distributed in various tissues, with the highest content in the stomach, intestine, liver and kidney. The concentrations of selenium in 24 h liver and kidney tissues were (6.14 ± 0.87) And (6.93 ± 0.94) μg.g-1 respectively, while the selenium concentration in the blood at the same time point was (4.43 ± 1.65) μg.mL-1. After 48 h, the selenium concentrations in other tissues were lower than those in selenium . Colorectal cancer nude mice can be seen 1 h after administration of prototype drugs rapidly distributed in various tissues, to 24 h kidney drug concentration peak, while other tissues significantly reduced drug concentrations to 48 h tumor can still be detected in higher drug concentrations . CONCLUSION: Oral selenide can be widely distributed in tumor-bearing nude mice and colon cancer after oral administration, and has certain selectivity for tumor tissue. The distribution of ethane selenide may be related to the metabolism and excretion of drugs.