中华眼镜蛇毒组份Ⅲ的药代动力学及组织分布研究

目的:观察中华眼镜蛇(Najanajaatra)蛇毒组份Ⅲ在兔体内的药代动力学过程和在小鼠体内的分布状况。方法:用氯胺-T法对眼镜蛇毒组份Ⅲ进行碘化标记,用放射性核素示踪动力法检测血液中的药物浓度,以放射性参与量(脏器与血液放射比)的比值作为组份Ⅲ在组织中分布的依据。结果:兔静脉注射眼镜蛇毒组份Ⅲ75、150和300μg／kg3个剂量后,快分布相半衰期T_1/2α为39.6-42.5min,慢分布相半衰期T_1/2β为16.8-17.3h,消除相半衰期T_1/2γ为21.7-22.1h。小鼠尾静脉注射¹²⁵Ⅰ]-组份Ⅲ后,2h及4h放射性参与量大于1的器官为肝脏、肾脏、肺脏、心脏和肌肉,其中以肾脏分布最高,且4h放射性参与量高于2h。结论:兔静脉注射组份Ⅲ3个剂量后,血药-时间曲线经3P87药动学程序拟合符合三房室模型特征,3个时相的半衰期各剂量组之间无显著差异,曲线下面积(AUC)与剂量成正比,表明药物在兔体内的分布和消除为一级线性动力学过程。小鼠静注组份Ⅲ后2h,以肾脏分布最高,肝脏与肺脏的放射性参与量也较高,尿中含量很高。

Pharmacokinetics and distribution of fraction Ⅲ isolated from Naja naja atra venom

AIM: To investigate the distribution in mice and pharmacokinetics in rabbits of fraction Ⅲ isolated from Naja naja atra venom. METHODS: Fraction Ⅲ was labelled with ¹²⁵Ⅰ] by chloramine-T method. The drug concentration in blood was determined by a radionuclide tracing kinetic methods. The distribution of ¹²⁵Ⅰ]-fraction Ⅲ in mice was determined based on the ratio of the relative incorporation of radioactivity in tissues to that in blood. RESULTS: In two and four hours after intravenous injection of fraction Ⅲ in mice, the organs in which the ratio of the radioactivity incorporation was bigger than 1 were liver, kidney, lung, heart and muscle, whth the maximun in kidney. After intravenous injection of fraction Ⅲ, with dosages of 75, 150 and 300 μg/kg, respectively, the T_1/2α, T_1/2β and T_1/2γ were 39.6-42.5 min, 16.8-17.3 h and 21.7-22.1 h, respectively. There was no significant difference between the different dosages. CONCLUSION: Fraction Ⅲ was mostly found in kidney, followed by liver and lung after intravenous administration in mice. The pharmacokinetics is in accordance with the feature of three atrioventricular modle. The AUC is in direct proportion to the dosage. It suggests that the distribution and clearance of the drug is a grade 1 linear kinetic process.