药物转运体在高原合理用药中的作用

Role of drug transporters in rational use of drugs at high altitude area

高原药代动力学是高原合理用药的重要依据,影响药代动力学参数改变的原因很多,以往的研究主要集中于缺氧对肝药酶的影响,鲜见对缺氧条件下药物转运体的研究。药物转运体是主动转运药物通过细胞膜进入体内和产生效应的关键因素,如多药耐药蛋白(multidrug resistance protein,MDR)、多药耐药相关蛋白(multidrug resistance associated protein,MRP)、乳腺癌耐药蛋白(breast cancer resistance protein,BCRP)、有机阴离子转运蛋白(organic anion transporter,OAT)、有机阳离子转运蛋白(organic cation transporter,OCT)、有机阴离子转运肽(organic anion-transporting polypeptide,OATP)、寡肽转运蛋白(qligopeptide transporter,PEPT)等,其广泛存在于小肠的绒毛上皮细胞、肾小管上皮细胞、肝细胞和胆管上皮细胞,在药物的吸收、分布、代谢和排泄各个环节发挥重要作用。缺氧时肠道药物转运体变化将影响药物的生物利用度;脏器中药物转运体变化将影响药物的分布范围,使药物的适应证发生改变,同样也可能增加药物不良反应的发生概率;肝、肾中药物转运体的表达发生改变将影响药物的代谢及排泄速率,使药物在体内的驻留时间发生改变,影响药物的半衰期。

Pharmacokinetics plays a key role in rational use of medicines. Many factors can affect the drug＇s pharmacokinetics. Previous studies mainly focused on the impact of hypoxia on hepatic drug metabolizing enzyme, but uncommon on drug transporters. Actually, drug transporter is a key factor for activation of the drugs transport across the cell membrane into the inside of cells, such as multidrug resistance protein （MDR）, breast cancer resistance protein （BCRP）, multidrug resistance associated protein （MRP）, organic cation transporter （OCT）, organic anion-transporting polypeptide （OATP）, organic anion transporter （OAT）, qligopeptide transporter （PEPT）,etc. They are widely present in the small intestine villus epithelial cells, renal tubular epithelial cells, hepatocytes and biliary epithelial cells. They play a very important role in drug absorption, distribution, metabolism and excretion. The changes in drug transporters under hypoxia in intestinal could affect the bioavailability of drugs; the changes in drug transporters in organs could affect drug＇s distribution, subsequent drug＇s indications and adverse reactions; the changes in drug transporters in liver and kidney could affect the metabolism and excretion rate of drugs, thereby the drug＇s residence time and half-life.