结构及基因多态性对他汀类药物药动学的影响

Structure and Gene Polymorphism Affect the Metabolism of Statins

他汀类药物是临床中治疗高胆固醇血症的一线药物。研究发现,不同的化学结构影响他汀类药物体内转运代谢的方式。化学结构的不同导致他汀药物的疏水性产生差异,从而影响药物体内的膜转运程度及组织亲和力,影响药物的体内吸收程度及在重要脏器的分布。他汀类药物的体内代谢主要与药物代谢酶相关,基因多态性影响药物代谢酶的活性及代谢能力。不同基因型对他汀类药物的体内代谢过程及降脂疗效可产生较大程度的影响。笔者从他汀类药物的结构出发,总结药物代谢酶尤其是肝药酶及膜转运体蛋白的基因多态性对他汀类药物体内代谢的影响,为更精准的使用他汀类药物,规避临床用药风险提供参考。

Statins are the main drugs for high cholesterol. The different chemical structures affect the metabolize way of statins. Different chemical structures of statins lead to differences in hydrophobicity and affect the degree of membrane transport and tissue affinity. The differences in hydrophobicity may influence the absorption of statins and the distribution in important organs. The metabolism of statins in vivo is mainly related to drug metabolizing enzymes. Gene polymorphism affects the activity and capacity of enzymes and may influence the lipid-lowering effect of statins. This paper reviews the transshipment and metabolic characteristics of statins. We summarize the gene polymorphism on the effect of drug metabolism and conduct the clinical prescription.