烟酸代谢物在潮红和肝毒性中的作用。

The role of nicotinic acid metabolites in flushing and hepatotoxicity.

机构信息

CVC Cardiovascular Medicine, University of Michigan, 1500 E Medical Center Drive SPC 5853, Ann Arbor, MI 48109-5853, USA.

出版信息

J Clin Lipidol. 2007 Jul;1(3):191-3. doi: 10.1016/j.jacl.2007.04.003. Epub 2007 Apr 20.

DOI:10.1016/j.jacl.2007.04.003

PMID:21291680

Abstract

Flushing and hepatotoxicity are important adverse effects of nicotinic acid. This article reviews the role of metabolism of nicotinic acid in the production of these side effects. The suggestion that nicotinic acid (NUA) formation produces flushing is traced to a correlation of flushing with NUA C(max) (maximal concentration) and the observation that aspirin inhibits NUA formation and flushing. The former does not establish causation and the latter can be explained by inhibition of prostaglandin formation. Recent characterization of the GPR109A receptor that mediates prostaglandin release by Langerhans cells to produce flushing has shown nicotinic acid, not NUA, is responsible. The suggestion that nicotinamide metabolites produce hepatotoxicity is not supported by any data. The mechanism of hepatotoxicity is unknown and a toxic metabolite of nicotinic acid has not been identified. Different nicotinic acid formulations produce different metabolite patterns due to nonlinear pharmacokinetics, but there is no evidence that these differences have any clinical importance.

摘要

潮红和肝毒性是烟酸的重要不良反应。本文综述了烟酸代谢在这些副作用产生中的作用。烟酸（NUA）形成产生潮红的观点可以追溯到潮红与 NUA C（max）（最大浓度）的相关性，以及观察到阿司匹林抑制 NUA 形成和潮红。前者不能确定因果关系，后者可以通过抑制前列腺素的形成来解释。最近对 GPR109A 受体的特征描述表明，该受体介导郎格汉斯细胞释放前列腺素以产生潮红，表明烟酸而不是 NUA 是导致潮红的原因。没有任何数据支持烟酰胺代谢物产生肝毒性的观点。肝毒性的机制尚不清楚，也没有鉴定出烟酸的有毒代谢物。由于非线性药代动力学，不同的烟酸制剂会产生不同的代谢物模式，但没有证据表明这些差异具有任何临床意义。