矽宁在人体内的药代动力学研究

Pharmacokinetic studies of Xinin in human blood

建立了高效液相色谱法测定人体全血中矽宁浓度。该法最低检测浓度为０．０１ｍｇ／Ｌ，平均回收率为９６．３％±０．４％，日内及日间的精密度（ＣＶ）分别为５．９％及８．９％。全血中矽宁浓度在０．０４～１２００ｍｇ／Ｌ时呈良好的线性关系。健康男性志愿者７名，口服单剂量矽宁１００ｍｇ后，其药代动力学过程符合二室一次吸收模型。该药在消化道内吸收较快，滞后时间为０．１８８ｈ，血浆浓度达峰时间为０．６９５ｈ，全血消除相半衰期（Ｔ）为６．２６３ｈ，表现分布容积为０．３ｍＬ／ｋｇ。

Xinin is a new antisilicotic drug and has been used recently in the treatment of silicotic patients. A method to determine the concentration of Xinin in whole blood by phase high performance liquid chromatography was established. A 250mm ×4. 6mm ID of Bondapak-C18 column and detecting at 254 nm was used.The mobil phase was acetonitrile-acetate buffer solution(pH 5)-methanol(74 : 18 : 8) at a flow rate of 1ml/min. The minimum detectable quantity of Xinin in whole blood was 0.01mg/L. The calibration curve of Xinin concentration is linear over the range of 0.04～1200mg/L with r=0.9973. Application of this method to study Xinin pharmacokinetics was investigated in seven volunteers following a single administration at the dose of 100mg orally. The whole blood concentration-time curve fit a two-compartment open model with following pharmaceutical parameters:T1/2α=0. 409h, T1/2β=6. 262h, T1/2ka=0. 267h, AUC=8439.5μg/(L.h),CLS=0.0002L/ (kg·h),T=0. 695h, C=2823. 9mg/ L.