發(fā)布時(shí)間：2018-02-26 21:55

  本文關(guān)鍵詞： SN-脂質(zhì)體 藥動學(xué) 組織分布 伊立替康　出處：《沈陽藥科大學(xué)學(xué)報(bào)》2016年04期 　論文類型：期刊論文

【摘要】：目的研究SN-38脂質(zhì)體大鼠體內(nèi)藥動學(xué)及小鼠組織分布學(xué)特征,為進(jìn)一步非臨床研究提供一定的實(shí)驗(yàn)基礎(chǔ)。方法以鹽酸伊立替康注射液(irinotecan,簡稱CPT-11)為參比制劑,大鼠尾靜脈單次給予不同劑量的SN-38脂質(zhì)體,于不同時(shí)間點(diǎn)眼框取血;小鼠尾靜脈給予單劑量的SN-38脂質(zhì)體,于2 h處死,取心、肝、脾、肺、腎等組織勻漿。并且建立HPLC法,用于大鼠血漿及小鼠組織樣品中SN-38的含量測定。結(jié)果低、中、高3種劑量的SN-38脂質(zhì)體在大鼠體內(nèi)均消除較快,其t1/2無明顯差異,AUC則隨劑量的增加而增加。小鼠尾靜脈注射SN-38脂質(zhì)體后,主要聚集在肝、脾、肺中,且其在心、腎組織中的含量低于對照組。結(jié)論 SN-38脂質(zhì)體在大鼠體內(nèi)呈線性動力學(xué)消除。小鼠組織分布結(jié)果表明其對于肝、脾等網(wǎng)狀內(nèi)皮細(xì)胞豐富的組織靶向性強(qiáng),能夠提高該器官的治療指數(shù);同時(shí)還可降低對心、腎組織的毒性及不良反應(yīng)。
[Abstract]:Objective to study the pharmacokinetics and histological distribution of SN-38 liposome in rats, and to provide an experimental basis for further non-clinical study. Methods Iritikang Hydrochloride injection (CPT-11) was used as a reference preparation. Rat caudal vein was given single dose of SN-38 liposome, and blood was taken from eye frame at different time points, and mice were given single dose of SN-38 liposome for 2 h. The homogenate of heart, liver, spleen, lung, kidney and so on were taken, and the HPLC method was established. It was used to determine the content of SN-38 in rat plasma and tissue samples of mice. The results showed that SN-38 liposomes of low, medium and high doses were eliminated rapidly in rats. There was no significant difference in t1 / 2 and AUC was increased with the increase of dose. After caudal vein injection of SN-38 liposome, it was mainly concentrated in liver, spleen, lung, and heart. Conclusion SN-38 liposomes were eliminated linearly in rats. The tissue distribution in mice showed that the liposomes were highly targeted to the liver, spleen and other reticuloendothelial cells. It can improve the therapeutic index of the organ and decrease the toxicity and adverse reaction to heart and kidney.
【作者單位】： 沈陽藥科大學(xué)藥學(xué)院;本溪高中;
【分類號】：R965
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本文編號：1539828