二氢吡啶类钙拮抗剂的吸收、分布、代谢与排泄研究概况

二氢吡啶类药物是重要的钙离子通道拮抗剂,是目前临床应用较广的一类抗高血压药物.本文从该类药物的吸收、分布、代谢与排泄方面综述其药代动力学特征,为新药研发及临床应用提供依据.二氢吡啶类药物脂溶性好,易透过细胞膜,但首过效应较强,会对其生物利用度产生较大的影响;表观分布容积较大,血浆蛋白结合率高,可迅速向各组织分布,主要分布于肝、肾等血流速率快的组织;在体内主要经细胞色素P450酶(CYPs)代谢,而CYP3A是参与其代谢的主要亚型,Ⅰ相代谢包括二氢吡啶环氧化、酯健水解及羟化反应,Ⅱ相代谢以葡萄糖醛酸结合为主;主要以代谢产物的形式从尿液、胆汁、粪便排泄,原型药物的排泄量极少.

Research overview in absorption, distribution, metabolism and excre- tion of dihydropyridine calcium antagonists

Dihydropyridines represent a class of the most important calcium antagonists which are widely used as antihypertensive drugs. In this review, we summarized the published meta- bolic and pharmacokinetic studies of dihydropyr- idines, including their absorption, distribution, metabolism and excretion in animals and hu- mans, to provide reference for drug development and clinical application. Dihydropyridines are highly lipophilic with good membrane permeabil- ity, but subjected to extensive first-pass effect which affects their oral bioavailability; these drugs, with large apparent volume of distribu- tion and high plasma protein binding rate, can rapidly distribute to various tissues, and the fastblood flow rate tissues such as liver and kidney are the main distribution tissues; they are me- tabolized mainly by cytochrome P450 enzymes （CYPs）, especially CYP3A isoforms. Oxidation of the 1,4-dihydropyridine into pyridine, ester hydrolysis and hydroxylation are involved in phase I metabolism, the phase II metabolism is glucuronidation; they are excreted from urine, bile and feces mainly in the form of metabolites, the excretion of parent drug is little.