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

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. 12 mg·kg^-1 iv后t_1/2α为0.13 h，t_1/2β为3.8 h；12和48 mg·kg^-1 im 后t_1/2β为7.1和4.1 h，AUC与剂量呈正比，CL_S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±0.3 nmol·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，2 d排出约86%.

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

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 ［¹²⁵I］vNGF in dorsal root ganglion of embryo chicken demonstrated growing of process around ganglion in vitro. Concentrations of bound ［¹²⁵I］vNGF, free ［¹²⁵I］vNGF, and ¹²⁵I-labeled degradation products were determined by size exclusive high performance liquid chromatography (SHPLC). Terminal half-lives of free ［¹²⁵I］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 ［¹²⁵I］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.