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猕猴静脉推注加滴注重组人碱性成纤维细胞生长因子后的药代动力学 被引量:6

Pharmacokinetics of recombinant human basic fibroblast growth factor following intravenous bolus plus infusion in rhesus monkey
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摘要 目的 研究猕猴静脉推注加滴注 (2 0 %∶80 % )10、2 0和 4 0 μg·kg- 1重组人碱性成纤维细胞生长因子 (rhbFGF)后血清抗原浓度 时间变化和药代动力学并与静脉推注比较。方法 ELISA法 ,测定浓度的专一性、灵敏度、重现性和测定范围 ,血清回收率和精密度均良好。结果 猕猴血清内源性水平(14 4± 10 1)ng·L- 1;静脉推注后即刻浓度最高 ,分别为 (33± 16 ) ,(5 6± 8)和 (91± 2 8) μg·L- 1,滴注期间稳定在 2 2~ 2 7,37~ 4 4和 6 3~ 6 5 μg·L- 1,提示控制药量和滴注速率可使浓度维持在不同水平。停药后浓度迅速下降 ,平均末端相半衰期 (t1/ 2 )为 2 .6~2 .9h。AUC( 0~∞ ) 随剂量成正比增大 ,全身清除率Cls不变。结论 在给药量范围内表现为线性药代动力学。静脉推注药代动力学与推注加滴注组相近。 AIM To study concentration time profiles and pharmacokinetics of recombinant human basic fibroblast growth factor (rhbFGF) following intravenous bolus injection plus infusion of the drug (20%∶80%) at 10, 20 and 40 μg·kg -1 and compared with bolus injection in rhesus monkey. METHODS The specificity, sensitivity, precision and accuracy of determination by enzyme labeled immunosorbent assay were satisfied. RESULTS The endogenous level of bFGF was (144±101)ng·L -1 in plasma. c max of (33±16), (56±8) and (91±28)μg·L -1 , respectively, was observed immediately after injection. Levels maintained at 22-27, 37-44, 63-65 μg·L -1 , respectively during infusion. Concentration rapidly decreased after the end of administration, with an average terminal t 1/2 of 2.6-2.9 h. AUC (0-∞) increased proportional with dose, and systemic clearance Cl s was closed among doses. CONCLUSION In dosage range studied pharmacokinetic behavior appeared as linear kinetic. The parameters of the drug after bolus were similar to bolus plus infusion.
出处 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2002年第3期220-222,共3页 Chinese Journal of Pharmacology and Toxicology
基金 国家自然科学基金重点项目 (39930 180 )~~
关键词 猕猴 静脉推注 静脉滴注 重组人碱性成纤维细胞生长因子 药代动力学 酶联免疫吸附测定 recombinant human basic fibroblast growth factor monkey, rhesus pharmacokinetics enzyme labeled immunosorbent assay
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参考文献3

  • 1[1]Martinez G,Di Giacomo C,Sorrenti V,Carnazza ML,Ragusa N,Barcellona ML,et al.Fibroblast growth factor-2 and transforming growth factor-beta1 immunostaining in rat brain after cerebral postischemic reperfusion[J].J Neurosci Res,2001,63(2):136-142. 被引量:1
  • 2[2]Fawcett JW.Spinal cord repair: from experimental models to human application[J].Spinal Cord,1998,36(12):811-817. 被引量:1
  • 3[3]Mazue G,Bertolero F,Jacob C,Sarmientos P,Roncucci R.Preclinical and clinical studies with recombinant human basic fibroblast growth factor[J].Ann N Y Acad Sci,1991,638:329-340. 被引量:1

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