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

Abstract

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

CLC Number:

R969.1
R972

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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