广州医科大学学报

目的：探讨眼镜蛇毒（Ｎａｊａ ｎａｊａ ａｔｒａ）蛇毒组分Ⅲ在小鼠体内的分布状况和在兔体内的药代动力学过程。方法：用氯胺－Ｔ法对眼镜蛇毒组分Ⅲ进行１２５Ｉ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）的比值作为组分Ⅲ在组织中分布的依据。结果：小鼠尾静脉注射１２５Ｉ－组分Ⅲ后，２ｈ及 ４ ｈ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 ４ ｈ放射性参与量高于２ｈ。兔静脉注射眼镜蛇毒组分Ⅲ７５、１５０和３００μｇ／ｋｇ三个剂量后，快分布相半衰期Ｔ１／２α为３９．６～４２．５ｍｉｎ，慢性分布相半衰期Ｔ１／２β为１６．８～１７．３ ｈｒ，消除相半衰期Ｔ１／２γ为２１．７～２２．１ｈｒ。结论：小鼠静注组分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。兔静脉注射组分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，三个时相的半衰期各剂量组之间无显著性差异，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。

Objective:To investigate the distribution of Fraction Ⅲ isolated from Naja naja atra venom in mice and its pharmacokinetics in rabbits. Methods: Fraction Ⅲ of Naja naja atra venom was labelled with 125I by chloramine-T method. The drug concentration in blood was determined by a radionuclide tracing kinetic method. The distribution of 125 I-Fraction Ⅲ in mice was determined based on the ratio of the relative incorporation of radioactivity in tissues to that in blood. Results: Two and four hours after intravenous injection of the Fraction Ⅲ in mice, the organs in which the ratio of the radioactivity incorporation was bigger than 1 were kidney, liver, lung, heart and muscle, with the maximum in kidney. After intravenous injection of Fraction Ⅲ, with dosages of 75, 150 and 300 μｇ/kg respectively, the T1/2α, T1/2 β and T1/2 γ were 39. 6～42. 5min, 16. 8～ 17. 3 h and 21. 7～22. 1 h, respectively. There was no significant difference between the different dosages. Conclusion: The Fraction Ⅲ was mostly found in kidney,followed by liver and lung after intravenous administration in mice. The pharmacokinetics was in accordance with the feature of three atrioventricular model. The AUC was in direct proportion to the dosage. It suggested that the distribution and clearance of the drug was a Grade 1 Linear kinetic process.