Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland.
Institute of Pharmacology and Toxicology, Rostock University Medical Center, 18057 Rostock, Germany.
Int J Mol Sci. 2024 Jun 25;25(13):6926. doi: 10.3390/ijms25136926.
Membrane transporters interact not only with endogenous substrates but are also engaged in the transport of xenobiotics, including drugs. While the coordinated function of uptake (solute carrier family-SLC and SLCO) and efflux (ATP-binding cassette family-ABC, multidrug and toxic compound extrusion family-MATE) transporter system allows vectorial drug transport, efflux carriers alone achieve barrier functions. The modulation of transport functions was proved to be effective in the treatment strategies of various pathological states. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are the drugs most widely applied in clinical practice, especially in the treatment of diabetes mellitus and heart failure. Sodium taurocholate co-transporting polypeptide (NTCP) serves as virus particles (HBV/HDV) carrier, and inhibition of its function is applied in the treatment of hepatitis B and hepatitis D by myrcludex B. Inherited cholestatic diseases, such as Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) can be treated by odevixibat and maralixibat, which inhibit activity of apical sodium-dependent bile salt transporter (ASBT). Probenecid can be considered to increase uric acid excretion in the urine mainly via the inhibition of urate transporter 1 (URAT1), and due to pharmacokinetic interactions involving organic anion transporters 1 and 3 (OAT1 and OAT3), it modifies renal excretion of penicillins or ciprofloxacin as well as nephrotoxicity of cidofovir. This review discusses clinically approved drugs that affect membrane/drug transporter function.
膜转运蛋白不仅与内源性底物相互作用，还参与包括药物在内的外源性物质的转运。虽然摄取（溶质载体家族-SLC 和 SLCO）和外排（ATP 结合盒家族-ABC、多药和毒性化合物外排家族-MATE）转运体系统的协调功能允许载体药物转运，但外排载体本身可实现屏障功能。转运功能的调节已被证明在各种病理状态的治疗策略中是有效的。钠-葡萄糖共转运蛋白-2（SGLT2）抑制剂是临床实践中应用最广泛的药物，特别是在治疗糖尿病和心力衰竭方面。牛磺胆酸钠共转运蛋白（NTCP）作为病毒颗粒（HBV/HDV）的载体，其功能的抑制被应用于乙型肝炎和丁型肝炎的治疗中，如米利尤昔单抗 B。遗传性胆汁淤积性疾病，如 Alagille 综合征（ALGS）和进行性家族性肝内胆汁淤积症（PFIC），可以通过奥贝胆酸和马洛胆酸治疗，它们抑制顶端钠依赖性胆汁盐转运蛋白（ASBT）的活性。丙磺舒可被认为主要通过抑制尿酸转运蛋白 1（URAT1）增加尿液中的尿酸排泄，并且由于涉及有机阴离子转运蛋白 1 和 3（OAT1 和 OAT3）的药代动力学相互作用，它还可改变青霉素或环丙沙星的肾脏排泄以及更昔洛韦的肾毒性。本综述讨论了影响膜/药物转运蛋白功能的临床批准药物。
