藥物轉(zhuǎn)運(yùn)體作為調(diào)控藥物跨膜轉(zhuǎn)運(yùn)的核心膜蛋白，通過(guò)ATP水解或離子/濃度梯度驅(qū)動(dòng)的運(yùn)輸機(jī)制，介導(dǎo)藥物、內(nèi)源性生物活性分子及外源性毒素的跨膜轉(zhuǎn)運(yùn)過(guò)程，在藥物吸收、分布、代謝與排泄過(guò)程中發(fā)揮關(guān)鍵作用。這類(lèi)蛋白主要分為ATP結(jié)合盒轉(zhuǎn)運(yùn)體和溶質(zhì)載體轉(zhuǎn)運(yùn)體兩大家族。研究表明，轉(zhuǎn)運(yùn)體基因的單核苷酸多態(tài)性可通過(guò)改變其表達(dá)水平、轉(zhuǎn)運(yùn)活性或底物親和力，顯著影響藥物的動(dòng)力學(xué)特征及療效與安全性。近年來(lái)，隨著藥物基因組學(xué)的快速發(fā)展，相關(guān)研究已從分子機(jī)制解析逐步延伸至臨床實(shí)踐。系統(tǒng)綜述與藥物處置密切相關(guān)的轉(zhuǎn)運(yùn)體基因多態(tài)性，重點(diǎn)解析其對(duì)藥動(dòng)學(xué)參數(shù)、臨床療效及不良反應(yīng)的影響，旨在為精準(zhǔn)用藥提供遺傳學(xué)依據(jù)，推動(dòng)個(gè)體化治療策略的優(yōu)化。

Drug transporters, as core membrane proteins regulating the transmembrane transport of drugs, mediate the transmembrane transport of drugs, endogenous bioactive molecules, and exogenous toxins through ATP hydrolysis or ion/concentration gradient-driven transport mechanisms, playing a crucial role in drug absorption, distribution, metabolism, and excretion. These proteins are mainly classified into two families: ATP-binding cassette transporters and solute carrier transporters. Studies have shown that single nucleotide polymorphisms in transporter genes can significantly affect the pharmacokinetic characteristics and efficacy and safety of drugs by altering their expression levels, transport activities, or substrate affinities. In recent years, with the rapid development of pharmacogenomics, related research has gradually extended from molecular mechanism analysis to clinical practice. This systematic review focuses on the polymorphisms of transporters closely related to drug disposition, particularly their impact on pharmacokinetic parameters, clinical efficacy, and adverse reactions, aiming to provide genetic evidence for precision medicine and promote the optimization of personalized therapeutic strategies.

R969.3

藥物成藥性評(píng)價(jià)與系統(tǒng)轉(zhuǎn)化全國(guó)重點(diǎn)實(shí)驗(yàn)室(天津藥物研究院)自主研究課題資助項(xiàng)目(712024001)