摘要
目的探讨VEGF125-136在家兔体内的药代动力学。方法采用放射性核素99Tcm对VEGF125-136进行间接标记。测定6只家兔静脉注射37MBq99Tcm-VEGF125-136后不同时间血浆中药物的放射性浓度,用DAS软件编制放射性浓度-时间曲线,并计算药代动力学参数。结果99Tcm-VEGF125-136的放射化学纯度大于97%,99Tcm-VEGF125-136在家兔体内的代谢符合三室模型,快分布相半衰期(t1/2α)为(5.327±2.351)min,慢分布相半衰期(t1/2β)为(26.446±6.502)min,消除相半衰期(t1/2γ)为(304.41±216.811)min,转运速率常数K10、K12、K21、K31及K13分别为(0.047±0.034)、(40.65±68.54)、(0.111±0.058)、(0.111±0.058)min-1及(0.002±0.004)min-1,清除率(CL)为(4.00±1.00)ml/min。结论VEGF125-136在家兔体内的药代动力学符合三室模型,且血液清除快而周边血管丰富的组织停留时间相对较长。
Objective To investigate the pharmacokinetics of a 12-amino-acid residue peptide of vascular endothelial growth factor （VEGF, 125-136） in rabbits. Methods VEGF125-136 was indirectly labeled with 99Tern. After a single dose of 37 MBq of ^99Tc^m-VEGF125-136 was injected intravenously in 6 rabbits, the radioactive concentrations at different sampling times were determined. Then the plasma radioactive concentrationtime curve was drawn and pharmacokinetics parameters were calculated with DAS computer program. Results The radiochemistry purity of ^99Tc^m-VEGF125-136 was more than 97%, the radioactive concentrationtime curve of ^99Tc^m-VEGF125-136 was fitted to a three-compartment model with the main pharmacokinetic parameters as follows ： t1/2α, t1/2β and t1/2γ were （5. 327 ± 2.351 ）, （26. 446 ＋ 6. 502 ） and （ 304.41 ±216.811 ） min respectively. CL, K10, K12, K21, K31 and K13 were （4.00 ± 1.00） ml/min, （0. 047 ± 0. 034） min^-1, （40.65 ±68.54） min^-1, （0. 111 ±0.058） min^-1, （0. 111 ±0.058） min^-1 and （0.002 ±0.004） min^-1 respectively. Conclusion The pharmacokinetics is fitted to three compartment model in rabbits. VEGF125-136 can be cleared quickly from blood and its detention time in target tissue is long.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2007年第18期1746-1748,共3页
Journal of Third Military Medical University
基金
国家自然科学基金(30400114)
第三军医大学科研基金(2004)~~
关键词
多肽
VEGF
锝放射性同位素
药代动力学
家兔
peptide
vascular endothelial growth factor
^ 99 Technetium^m
pharmacoklnetlcs
rabbits
