摘要
目的:考察小鼠静脉注射G蛋白抑制肽GCIP-27后药动学情况。方法:125I-GCIP采用氯甘脲法标记,血浆中GCIP的浓度采用同位素示踪法结合三氯醋酸(TCA)沉淀法或低分子量SDS-PAGE电泳法测定。结果:GCIP-27在小鼠体内按一级动力学代谢,并呈三室开放模型;静脉注射125I-GCIP90μg.kg-1后,电泳法和酸沉法测得t1/2α、t1/2β、t1/2γ分别为0.009、0.245、2.054h和0.025、0.306、2.323h;tmax均为0.0333h,平均血浆清除率分别为0.295、0.322L.h-1.kg-1,表观分布容积分别为0.559、1.29L.kg-1,体内平均滞留时间分别为2.353、2.515h。结论:GCIP-27在小鼠体内血药浓度下降快,分布快,自中央室迅速向周边室分布;消除、代谢缓慢。本研究结果可为GCIP-27的剂型设计和药效学研究提供重要依据。
OBJECTIVE： To study the pharmacokinetics in mice after intravenous injection of GCIP - 27. METHODS： ^125I - GCIP was labeled by Iodogen method. The plasma concentration of GCIP was determined by isotope tracer method in combination with trichloroacetic acid （TCA） precipitation method or low molecular weight SDS-PAGE method. RESULTS： The Plasma concentration- time curves of GCIP 27 in mice conformed to three- compartment open model of first order kinetics. After intravenous injection of ^125I GCIP at a dose of 90μg . kg^-1, t 1/2α t 1/2β, t 1/2γ determined by SDS- PAGE method were 0.009, 0.245 and 2.054 h, respectively, and by TCA method were 0.025, 0.306 and 2.323 h, respectively, t for both methods was 0.033 3 h, with mean plasma clearance of 0. 295 vs. 0.322 L . h^-1 . kg^-1, apparent volume of distribution of 0.559 vs. 1.29 L . kg^ -1 and mean residence time of 2.353 vs. 2.515 h in mouse. CONCLUSION： The plasma concentration of GCIP- 27 decreased rapidly and distributed quickly from central compartment to peripheral compartment but which was eliminated and metabolized slowly in mice. Our studies serve important reference for the dosage form design and research on the pharmacodynamics of GCIP - 27.
出处
《中国药房》
CAS
CSCD
北大核心
2008年第4期266-268,共3页
China Pharmacy
