中西藥交互作用體內－體外試驗模型之建立及相關性探討 (2-1)
李珮端
中國醫藥大學
國人近年來在用藥習慣上，除了西藥外，亦常同時服用中藥。此種非經同一醫師處方而中西藥併用的特殊用藥習慣，隱藏著發生交互作用的風險。目前可供快速大量篩測中西藥交互作用的簡易體外-體內關聯模型仍極有限。本計畫擬以治療指數狹窄的 cyclosporine (CSP) 與methotrexate (MTX) 為西藥模型藥物，分別代表 P-glycoprotein (P-gp) 與 multidrug resistance proteins (MRPs) 之受質，而以食品與藥品中常見之甘草為中藥的模型藥物，以此兩種模型藥物進行中西藥交互作用的體內、體外試驗及相關性探討，期能建立簡易體外-體內關聯模型，提供藥物交互作用發生風險之快速評估平台。
本研究第一年將進行體內實驗，擬以大白鼠為模型，探討單劑量及多劑量併服甘草水煎劑、甘草酸及芍藥甘草湯對 CSP 及 MTX 藥物動力學之影響。第二年進行體外試驗，將以 Caco-2 探討甘草水煎劑、甘草酸、甘草次酸及芍藥甘草湯對 P-gp 與 MRP2 螢光受質運輸及基因表現的影響，並進一步比對體內、體外試驗的結果，探討其相關性，建立以 Caco-2 細胞為篩測模型，探討中藥與運輸蛋白P-gp、MRP2 相關的中西藥交互作用發生機率。此一結果除能提供臨床醫師與藥師，中西藥交互作用發生風險的訊息外，亦能提供開創中西藥合併治療的利基之資訊。對中藥之用藥安全與中藥新藥開發均極具意義。
關鍵字：中西藥交互作用、甘草、甘草酸、中藥方劑、體內－體外相關性、P-醣蛋白、多重耐藥性蛋白。
Establishment and evaluation of an in vivo-in vitro model for herb-drug interaction (2-1)
Pei-Dawn Lee Chao
China Medical University
In recent years, western medicines and Chinese herbs are often used concurrently in Taiwan. There are hidden risks of herb-drug interactions. Till now, no in vitro model was available for fast screening of herb-drug interaction. In this study, cyclosporine (CSP) and methotrexate (MTX) will be used as model drugs for substrates of P-glycoprotein (P-gp) and multidrug resistance proteins (MRPs), respectively. For the first year, the effects of single dose coadministration and multiple-dose pretreatment of licorice decoction (LD), glycyrrhizin (GZ) and two prescriptions containing licorice (P1 and P2) on the pharmacokinetics of CSP and MTX in rats will be investigated. For the second year, Caco-2 cells will be employed for the in vitro study. The influence on the transport of fluorescent substrates and gene expression of P-gp and MRP2 in Caco-2 cells by LD, GZ, glycyrrhetic acid (GA), P1 and P2 will be investigated. By correlating the in vivo-in vitro results, we anticipate to establish an in vitro fast screening model for herb-drug interaction. Hopefully, through this study, the risks of herb-drug interactions could be reduced and furthermore, beneficial combined therapy with herbs and western medicine would be developed.
關鍵字：herb-drug interaction; licorice; Chinese medicine prescription; in vivo-iv vitro correlation; P-glycoprotein; multidrug resistance proteins.
