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Archive > Volume 11 Issue 1 > 2019,11(1):92-97. DOI:10.1016/j.chmed.2018.10.002 Prev Next

基于藥代動(dòng)力學(xué)和熒光光譜研究監(jiān)測(cè)聯(lián)合用藥中游離態(tài)華法林

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Monitoring unbound warfarin in drug combination therapy by pharmacokinetics and fluorospectrometry

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    摘要:
    目的：藥物游離態(tài)濃度影響其療效，因此聯(lián)合用藥過(guò)程中檢測(cè)游離態(tài)藥物濃度十分必要。本研究將體內(nèi)藥代動(dòng)力學(xué)方法結(jié)合體外熒光光譜技術(shù)探討丹紅注射液(DHI)對(duì)體內(nèi)游離態(tài)華發(fā)林濃度影響。方法：采用微透析串聯(lián)LC-MS/MS技術(shù)考察丹紅注射液對(duì)游離態(tài)華法林藥代動(dòng)力學(xué)屬性影響；應(yīng)用熒光光譜技術(shù)研究DHI和丹酚酸B (SaB)對(duì)華法林與牛血清白蛋白(BSA)相互作用影響。結(jié)果：DHI與華法林聯(lián)合給藥組華法林AUC0-tn值高于華法林單獨(dú)組，表明DHI增加大鼠血液中游離態(tài)華法林濃度，這可能由于DHI及其成分與華法林競(jìng)爭(zhēng)競(jìng)爭(zhēng)性結(jié)合血清白蛋白。熒光光研究證明了該競(jìng)爭(zhēng)過(guò)程。結(jié)論：DHI與華法林的聯(lián)合用藥可以促進(jìn)華法林從血清白蛋白中的釋放。

    Abstract:
    Objective Monitoring the unbound drug concentration in blood in combination therapy is necessary, because its concentration determines the efficacy of drug therapy. This study was designed to explore the effect of Dan Hong Injection (DHI) on the unbound warfarin using two approaches including an in vivo pharmacokinetic and in vitro fluorescence studies. Methods The effect of DHI on the pharmacokinetic properties of the unbound warfarin was investigated by a microdialysis sampling method coupled with LC-MS/MS. The effect of DHI and salvianolic acid B (SaB) on warfarin binding with bovine serum albumin (BSA) was conducted by fluorescence spectrometry. Results The AUC0-tn of warfarin with DHI group was higher than that of warfarin alone group. The result showed that DHI could increase the concentration of unbound warfarin in rat blood, which may be due to the competition between warfarin and DHI as well as some its components binding to serum albumin. The competition process was demonstrated by fluorescence study. Conclusion Combination therapy of DHI with warfarin could enhance the release profile of warfarin from serum protein.

    關(guān)鍵詞:
    丹紅注射液;熒光光譜研究;微透析;藥代動(dòng)力學(xué);游離態(tài)華法林

    Keywords:


    Project Supported:
    This work was supported by Program for Changjiang Scholars and Innovative Research Team in University (No. IRT_14R41), Tianjin Research Program of Application Foundation and Advanced Technology (15JCYBJC29300).

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