蛇毒神经生长因子在大鼠体内的药物代谢动力学与周围神经分布  

Pharmacokinetics of venom neural growth factor in rats and its distribution in peripheral neural tissues

作　　者：刘秀文[1] 汤仲明[1] 柴彪新[1] 吕秋军[1] 汪家政[1] 

机构地区：[1]军事医学科学院放射医学研究所

出　　处：《中国药理学与毒理学杂志》1998年第3期215-220,共6页Chinese Journal of Pharmacology and Toxicology

摘　　要：用［１２５Ｉ］标记结合高效液相色谱法和酸沉法研究大鼠体内蛇毒神经生长因子（ｖＮＧＦ）药物代谢动力学．［１２５Ｉ］ｖＮＧＦ体外有刺激神经突起生长活性．药后血清存在游离和结合［１２５Ｉ］ｖＮＧＦ及［１２５Ｉ］降解物．１２ｍｇ·ｋｇ－１ｉｖ后ｔ１／２α为０．１３ｈ，ｔ１／２β为３．８ｈ；１２和４８ｍｇ·ｋｇ－１ｉｍ后ｔ１／２β为７．１和４．１ｈ，ＡＵＣ与剂量呈正比，ＣＬＳ相近，生物利用度为０．６２．体外［１２５Ｉ］ｖＮＧＦ与血清最大结合率２４．６％±０．４％，平衡解离常数３．２±０．３ｎｍｏｌ·Ｌ－１．ｉｍ后颈上神经节，注药侧和对侧坐骨神经放射性明显高于血清，注药侧最高，不被１００倍非标ｖＮＧＦ抑制．主要经尿排泄，２ｄ排出约８６％．Serum concentrationtime profiles of venom neural growth factor (vNGF), a 13 kDa alkaline protein purified from Cobra sinica, was studied in rats after iv or im injection in rats. Bioassay of [125I]vNGF in dorsal root ganglion of embryo chicken demonstrated growing of process around ganglion in vitro. Concentrations of bound [125I]vNGF, free [125I]vNGF, and 125Ilabeled degradation products were determined by size exclusive high performance liquid chromatography (SHPLC). Terminal halflives of free [125I]vNGF following iv 12 mg·kg1, or im 12, 48 mg·kg1were 3.8, 7.1 and 4.1 h, respectively. AUC increased with dose while CLS was similar after intramuscular injection. Bioavailability was 0.62 after intramuscular injection. Maximal percentage of serum bound [125I]vNGF in vitro was 24.6±0.4% and equilibrium dissociation constant (Kd) was 3.2±0.3 nmol·L1. Levels of acid precipitable radioactivity in sciatic nerve of the injected side, the opposite side and in superior cervical ganglion were higher than that in serum, which were not inhibited by the addition of 100fold nonlabeled vNGF. Eightysix percentage was excreted within 2 days and the major excretion route was urinary system.

关 键 词：蛇毒 神经生长因子 药代动力学 周围神经 分布 

分 类 号：R969.1[医药卫生—药理学] R931.74[医药卫生—药学]