[關(guān)鍵詞]
[摘要]
疾病狀態(tài)下藥物代謝酶和藥物轉(zhuǎn)運(yùn)體的異常調(diào)控會(huì)引起藥物動(dòng)力學(xué)過程的改變,進(jìn)而影響藥物療效,甚至增加不良反應(yīng)發(fā)生的風(fēng)險(xiǎn)。代謝酶/轉(zhuǎn)運(yùn)體異常調(diào)控的機(jī)制主要涉及炎癥相關(guān)的信號(hào)通路/核受體、表觀遺傳修飾和蛋白質(zhì)翻譯后修飾等。系統(tǒng)回顧并總結(jié)了幾類主要常見疾病狀態(tài)下的藥物代謝酶/轉(zhuǎn)運(yùn)體的調(diào)控變化及相關(guān)機(jī)制,同時(shí)介紹了生理藥動(dòng)學(xué)模型在指導(dǎo)疾病患者臨床合理用藥方面的應(yīng)用,以期為基于疾病狀態(tài)下藥物代謝酶/轉(zhuǎn)運(yùn)體的安全有效的個(gè)體化用藥提供借鑒和思路。
[Key word]
[Abstract]
Dysregulation of drug metabolizing enzymes and transporters (DMET) during diseases leads to altered pharmacokinetics.It has profound impact on drug safety and efficacy.The mechanisms of this dysregulation include inflammation associated signal pathway/nuclear receptor,epigenetic regulation and post-translational modification.This article reviews the regulation of DMET under disease status and its related mechanisms.The application of physiologically-based pharmacokinetic model in rational drug usage in patients is also summarized.Our work will benefit personalized medicine according to DMET phenotype.
[中圖分類號(hào)]
[基金項(xiàng)目]
國(guó)家自然科學(xué)基金(81573494,81803625,81573496);江蘇省自然科學(xué)基金(BK20160076,BK20180558)