Benowitz Neal L, Pomerleau Ovide F, Pomerleau Cynthia S, Jacob Peyton
Department of Medicine, University of California San Francisco, San Francisco, CA 94143-1220, USA.
Nicotine Tob Res. 2003 Oct;5(5):621-4. doi: 10.1080/1462220031000158717.
The rate of nicotine metabolism is hypothesized to be a determinant of how much a person smokes. That is, rapid metabolizers would be expected to need more nicotine and, therefore, smoke more than slow metabolizers. Nicotine is metabolized extensively by the liver enzyme CYP2A6, primarily to cotinine. Cotinine is itself metabolized by CYP2A6 to 3'-hydroxycotinine (3-HC). The ratio of metabolite to parent (i.e., 3-HC:cotinine) would be expected to reflect CYP2A6 activity. We measured the ratio of 3-HC:cotinine in the urine of 72 smokers. This ratio was significantly correlated with the number of cigarettes smoked per day (r=.33, p=.005), though not with the Fagerström Test for Nicotine Dependence. This finding supports the hypothesis that the rate of nicotine metabolism is a determinant of the level of cigarette consumption and supports the use of the 3-HC:cotinine ratio as a noninvasive marker of nicotine metabolism.
尼古丁代谢速率被假定为一个人吸烟量的决定因素。也就是说，预计尼古丁快速代谢者比缓慢代谢者需要更多尼古丁，因此吸烟更多。尼古丁主要通过肝脏酶CYP2A6广泛代谢为可替宁。可替宁自身又被CYP2A6代谢为3'-羟基可替宁（3-HC）。代谢物与母体的比例（即3-HC:可替宁）预计能反映CYP2A6的活性。我们测量了72名吸烟者尿液中3-HC:可替宁的比例。该比例与每日吸烟支数显著相关（r = 0.33，p = 0.005），但与尼古丁依赖的法格斯特龙测试无关。这一发现支持了尼古丁代谢速率是香烟消费水平决定因素的假说，并支持将3-HC:可替宁比例用作尼古丁代谢的非侵入性标志物。
