Nakajima Miki, Kuroiwa Yukio, Yokoi Tsuyoshi
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi 13-1, Kanazawa 920-0934, Japan.
Drug Metab Rev. 2002 Nov;34(4):865-77. doi: 10.1081/dmr-120015696.
Nicotine is widely consumed throughout the world, and exerts a number of physiological effects. After nicotine is absorbed through the lungs by cigarette smoking, it undergoes extensive metabolism in humans. Nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. CYP2A6 can metabolize some pharmaceutical agents such as halothane, valproic acid, and fadrozole, and activate tobacco-specific nitrosamines. There are large interindividual differences in nicotine metabolism, and it has been found that the interindividual differences are attributed to the genetic polymorphisms of CYP2A6 gene. This review describes the techniques for determination of in vivo nicotine metabolism, characteristics of each human CYP2A6 alleles, and ethnic differences. The relationship between CYP2A6 genetic polymorphism and potency of nicotine metabolism, smoking behavior, and cancer risk are extensively reviewed. Finally, the usefulness of nicotine metabolism for phenotyping of CYP2A6 in individuals and implication of the significance of CYP2A6 genetic polymorphism in a clinical perspective are discussed.
尼古丁在全球范围内被广泛使用，并产生多种生理效应。吸烟时尼古丁通过肺部吸收后，在人体内经历广泛的代谢。尼古丁主要由细胞色素P450（CYP）2A6代谢为可替宁。CYP2A6可代谢一些药物，如氟烷、丙戊酸和法倔唑，并激活烟草特有的亚硝胺。尼古丁代谢存在较大的个体差异，已发现个体差异归因于CYP2A6基因的遗传多态性。本文综述了体内尼古丁代谢的测定技术、各人类CYP2A6等位基因的特征以及种族差异。广泛综述了CYP2A6基因多态性与尼古丁代谢能力、吸烟行为和癌症风险之间的关系。最后，讨论了尼古丁代谢在个体CYP2A6表型分析中的作用以及从临床角度看CYP2A6基因多态性的意义。
