二氢吡啶类钙拮抗剂的吸收、分布、代谢与排泄研究概况

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (8): 937-943.

二氢吡啶类钙拮抗剂的吸收、分布、代谢与排泄研究概况

王盼¹, 谢珊珊¹, 郭建军², 卜海之², 陈西敬¹

¹中国药科大学药物代谢研究中心,南京 210009,江苏;
²苏州圣苏新药开发有限公司,苏州215104,江苏

收稿日期:2013-01-25 修回日期:2013-07-08 出版日期:2013-08-26 发布日期:2013-07-31
通讯作者: 陈西敬,男,博士,教授,博士生导师,研究方向:药物代谢动力学。Tel: 025-83271286 E-mail: chenxi-lab@hotmail.com; 卜海之,男,博士,研究方向:药物代谢动力学。Tel: 025-67683276 E-mail: haizhi.bu@3dbiooptima.com
作者简介:王盼,女,硕士研究生,研究方向:药物代谢动力学。Tel: 025-83271286 E-mail: wangpan1128@126.com
基金资助:
江苏省药代动力学重点实验室提升项目(BM2012012);苏州科学技术局姑苏创新创业领军人才基金的资助(XG0826)

Research overview in absorption, distribution, metabolism and excretion of dihydropyridine calcium antagonists

WANG Pan¹, XIE Shan-shan¹, GUO Jian-jun², BU Hai-zhi², CHEN Xi-jing¹

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu, China;
²3D BioOptima Co., Ltd., Suzhou 215104, Jiangsu, China

Received:2013-01-25 Revised:2013-07-08 Online:2013-08-26 Published:2013-07-31

摘要/Abstract

摘要： 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。

关键词: 二氢吡啶类, 吸收, 分布, 代谢, 排泄

Abstract: Dihydropyridines represent a class of the most important calcium antagonists which are widely used as antihypertensive drugs. In this review, we summarized the published metabolic and pharmacokinetic studies of dihydropyridines, including their absorption, distribution, metabolism and excretion in animals and humans, to provide reference for drug development and clinical application. Dihydropyridines are highly lipophilic with good membrane permeability, but subjected to extensive first-pass effect which affects their oral bioavailability; these drugs, with large apparent volume of distribution and high plasma protein binding rate, can rapidly distribute to various tissues, and the fast blood flow rate tissues such as liver and kidney are the main distribution tissues; they are metabolized 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.

Key words: Dihydropyridines, Absorption, Distribution, Metabolism, Excretion

中图分类号:

R969.1
R972

王盼, 谢珊珊, 郭建军, 卜海之, 陈西敬. 二氢吡啶类钙拮抗剂的吸收、分布、代谢与排泄研究概况[J]. 中国临床药理学与治疗学, 2013, 18(8): 937-943.

WANG Pan, XIE Shan-shan, GUO Jian-jun, BU Hai-zhi, CHEN Xi-jing. Research overview in absorption, distribution, metabolism and excretion of dihydropyridine calcium antagonists[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(8): 937-943.

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