重组人ω-干扰素在金黄地鼠和Wistar大鼠体内的组织分布和排泄  

Tissue Distribution and Excretion of Recombinant Human Interferon-ω in Golden Hamsters and Wistar Rats

作　　者：宋艳霞[1] 陈知航[1] 单成启[1] 侯禹男[1] 陈微[1] 余长明[1] 汤仲明[1] 程远国[1] 

机构地区：[1]军事医学科学院微生物流行病研究所,北京100071

出　　处：《生物技术通讯》2007年第3期457-459,共3页Letters in Biotechnology

基　　金：国家高技术研究发展计划项目(2003AA208220和2003AA2Z347B)

摘　　要：目的:为进一步的临床试验提供重组人ω-干扰素(rhIFN-ω)的分布和排泄试验数据。方法:用125I同位素示踪法结合三氯醋酸(TCA)沉淀法测定各主要器官组织的总放射性浓度和酸沉淀部分放射性浓度,获得rhIFN-ω的尿粪排泄和胆汁排泄数据。结果:各主要器官组织的总放射性浓度AUC0-4h排序由大到小依次为:尿、胸腺、胆囊、膀胱、肾、肾上腺、肠内容物、肠淋巴结、空肠、肺脏、血清、卵巢、脾、肝、肌肉、心脏、骨髓/股骨、睾丸、脂肪、脑。皮下注射125I-rhIFN-ω后48h尿和粪的累计排出量分别达到注入放射量的87.9%±2.8%和4.0%±1.6%,尿粪合计排出量占注入放射性量的91.9%±2.1%,而皮下注射125I-rhIFN-ω后20h内胆汁排泄放射性量占注入放射性量的3.34%。结论:rhIFN-ω在泌尿系统分布比较高,与血清蛋白结合比较少,在脑、脂肪和肌肉等组织的药物浓度最低。rhIFN-ω主要以尿的形式排泄。Objective： To provide experimental information on the metabolism of recombinant human interferon-ω（rhlFN- ω） necessary for subsequent clinical trials. Methods： ^125I-rhOFN-ω was prepared by iodogen method. Tissue distribution and urinary, fecal, biliary excretion profiles of ^125I-rhIFN-ω in golden hamsters and Wistar rats were demonstrated by TCA precipitation and secHPLC method. Results： In order of total radioactivity concentration in organs/tissues for rhIFN-ω, it showed that urine〉thymus〉cholecyst〉bladder〉kidney〉adrenal gland〉intestinal contents〉lymphnodes〉jejunum〉lung〉serum〉ovary〉spleen〉liver〉muscles〉heart〉bone marrow〉testicle〉fat〉brain. Approximately 87.9%±2.8% or 4.0%±1.6% of the total administered radioactivity was recovered in urine or feces within 48 h after administration, respectively; while 3.34% into bile within 20 h after administration. Conclusion： The results suggested that ^125I-rhIFN-ω was distributed to organs/tissues rapidly and widely, although the radioactivity was relatively low because of rapid excretion. Urinary route was the dominant excretion one.

关 键 词：重组人 ω-干扰素 组织分布 排泄 

分 类 号：R969.1[医药卫生—药理学] R979.1[医药卫生—药学]