厚朴酚与和厚朴酚在大鼠体内的药代动力学

Pharmacokinetics Profile of Magnolol and Honokiol in Wistar Rats

目的 观察厚朴酚与和厚朴酚在Wistar大鼠体内的动力学过程。方法 用实验建立的RP -HPLC法测定大鼠灌胃给予上述两种成分后不同时间各组织和体液中药物的含量及其蛋白结合率 ,并计算其在血中的药代动力学。结果 建立的方法能够良好分离两种成分 ,浓度 -色谱响应间线性相关系数均 >0 .999,平均加样回收率 >90 % ;两种成分在大鼠体内代谢符合一级消除动力学二室开放模型 ,Cmax 分别为 0 .974和 0 .5 2 2mg·L-1,T1/ 2 β 为 3.136和 3.2 84h ,T1/ 2ka 为 0 .16 0和 0 .2 6 1h ;进入体内后 ,主要滞留于胃肠内 ,其他主要分布于肝、肺、肾组织中 ;血浆蛋白结合率分别为 6 8.5 4 %和 5 3.81% ;以粪排出为主 ,尿和胆汁排出量只有约 5 %。结论 厚朴酚与和厚朴酚吸收较差 ,进入循环后以肝代谢和肾排泄为主。

Aim To investigate the pharmacokinetics of magnolol and honokiol in Wistar rat tissue and body fluid.Methods The magnolol and honokiol were simultaneous determined within 15 minutes by a RP-HPLC method on the column C 18 ,a mobile phase consisted of methanol-water-acetic acid glacial(70∶30∶1) with 1ml/min,a detector 294nm with sensitivity 0.005 Aufs.Results There was good linear relationship between both the two drugs' concentration in serum and urine and chromatogram peak area.Two drugs were found to conform to a two compartment open-model with C max 0.974mg·L -1 and 0.522mg·L -1 ,T 1/2β 3.136h and 3.284h,T 1/2ka 0.160h and 0.261h.The drugs were found in many tissues after a single oral dose and the top-level tissue were stomach and intestine.The distributions of the drugs were most in liver,lung and kidney.68.54% of magnolol and 53.81% of honokiol in plasma were shown to be bound to protein.The two drugs were no good assimilation since the total excretion of the parent compound in faces were more than 50% of the dose,and in urine and bile less than 5%.Conclusion Magnolol and honokiol were not up to absorption,metabolized in liver and drained from kidney first.