重组人白细胞介素－3在小鼠体内的药代动力学及组织分布

用Ｉｏｄｏｇｅｎ法制备１２５Ｉ－γｈＩＬ－３。产品用ＳｅｐｈａｄｅｘＧ－５０凝胶过滤纯化。流出的组分用ＳＤＳ－ＰＡＧＥ测定纯度。选取放化纯度高于９５％的进行药代动力学研究。在ｉＶ剂量为５００、１０００及２５００ｎｇ·ｍｏｕｓｅ－１的１２５Ｉ－γｈＩＬ－３后，浓度－时间曲线按三房室模型拟合，其快分布相约为２ｍｉｎ。慢分布相约为５０ｍｉｎ。终末消除相为８ｈ左右。ＡＵＣ与剂量呈较好的线性关系（ｒ＝０．９９７０）。ｉｍ１２５Ｉ－γｈＩＬ－３１０００ｎｇ·ｍｏｕｓｅ－１后浓度一时间曲线符合一室一级吸收，绝对生物利用度为０．８８，达峰浓度，时间分别为４２．７６μｇ·Ｌ－１和０．５０ｈ。ｉｖ１５ｍｉｎ后，在肾脏中的浓度最高，２４ｈ内排出约８６％的标记药物。

Pharmacokinetics and tissue distribution of recombinant human interleukin-3 in mice

I-labeled recombinant human interleukin-3 (125 I-γhIL-3) was prepared by iodogen method. Product was purified by Sephadex G-50 gel filtration. Eluate fractions were identified by SDSPAGE. Radioactive 95% purified 125 I-γhIL-3 fractions were selected for pharmacokinetics study. Concentration-time curves after iv 500, 1000 and 2500 ng of 125I-γhIL-3·mouse-1 were fitted to a 3-compartment model: with a fast distribution phase T of 2 min, a slow distribution phase T of 50 min, and a terminal elimination T of 8h. AUC was linearly related to the dosage (r=0. 997). The bioavailability of 125I-γhIL-3 after im was 0.88. The highest level was observed at 15 min later in kidney. About 86% injected dose was excreted within 24 h.