Female sex and oral contraceptive use accelerate nicotine metabolism
Female sex and oral contraceptive use accelerate nicotine metabolism
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DOI：
10.1016/j.clpt.2006.01.008
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发表时间：
2006-05-01
影响因子：
6.7
通讯作者：
Jacob, Peyton, III
中科院分区：
文献类型：
--
作者：
Benowitz, Neal L.;Lessov-Schlaggar, Christina N.;Jacob, Peyton, III
背景：多项研究表明，女性吸烟者患肺癌的风险高于男性吸烟者。这可能与尼古丁代谢和相关吸烟行为的性别差异有关。这项研究检验了以下假设：女性比男性代谢尼古丁更快，并且在女性中，口服避孕药使用者比非口服避孕药使用者代谢尼古丁更快。方法。从北加州双胞胎登记处招募了 278 名健康的双胞胎志愿者和 16 名双胞胎的兄弟姐妹，他们接受了氘标记的尼古丁和可替宁的输注，并频繁进行血液采样。测量尼古丁和可替宁的血浆清除率、尼古丁对可替宁的清除率（细胞色素 P450 [CYP]2A6 活性的指标）以及反式 3'-羟基可替宁与可替宁的比率（CYP2A6 活性的另一个指标）。 结果：尼古丁和可替宁的清除率、尼古丁对可替宁的清除率以及女性反式-3'-羟基可替宁/可替宁比率显着高于男性（尼古丁清除率，男性为 15.6 +/- 4.3 mL (.) min(-1) (.) kg(-1)，女性为 18.8 +/- 6.6 mL (.) min(-1) (.) kg(-1)；P < .001）；服用口服避孕药的女性也高于未服用口服避孕药的女性（尼古丁清除率，服用口服避孕药的女性为 22.5 +/- 6.6 mL (.) min(-1) (.) kg(-1)，而未服用口服避孕药的女性为 17.6 +/- 6.1 mL (.) min(-1 .) kg(-1)；P < .05）。绝经或绝经后的女性与男性没有什么不同。在口服避孕药使用者中，服用复方避孕药和纯雌激素避孕药的尼古丁代谢加速，但服用纯孕激素避孕药的尼古丁代谢加速。结论：性激素影响尼古丁代谢。女性的尼古丁和可替宁代谢比男性更快，服用口服避孕药的女性比未服用口服避孕药的女性更快。尼古丁代谢加速似乎是雌激素的结果。尼古丁清除率与性别相关的差异可能会影响吸烟行为以及对尼古丁药物的反应，并且可能是尼古丁衍生致癌物代谢改变的标志。
Background: Several studies have reported that female smokers have a higher risk of lung cancer than male smokers. This could be related to sex differences in nicotine metabolism and related smoking behavior. This study tested the hypothesis that women metabolize nicotine more rapidly than men and that, among women, oral contraceptive users metabolize nicotine more rapidly than nonusers of oral contraceptives.Methods. Two hundred seventy-eight healthy volunteers who were twins and 16 who were siblings of twins, recruited from the Northern California Twin Registry, received an infusion of deuterium-labeled nicotine and cotinine with frequent blood sampling. The plasma clearances of nicotine and cotinine, the clearance of nicotine to cotinine (an index of cytochrome P450 [CYP] 2A6 activity), and the ratio of trans-3'-hydroxycotinine to cotinine (another indicator of CYP2A6 activity) were measured.Results: The clearances of nicotine and cotinine, the clearance of nicotine to cotinine, and the trans-3'-hydroxycotinine/cotinine ratio were significantly higher in women than in men (nicotine clearance, 15.6 +/- 4.3 mL (.) min(-1) (.) kg(-1) in men versus 18.8 +/- 6.6 mL (.) min(-1) (.) kg(-1) in women; P < .001); they were also higher among women taking oral contraceptives than in those who were not taking oral contraceptives (nicotine clearance, 22.5 +/- 6.6 mL (.) min(-1) (.) kg(-1) in women taking oral contraceptives versus 17.6 +/- 6.1 mL (.) min(-1 .) kg(-1) in those who were not; P < .05). Women who were menopausal or postmenopausal were not different from men. Among oral contraceptive users, nicotine metabolism was accelerated among those taking combined and estrogen-only contraceptives but not progesterone-only contraceptives.Conclusions: Sex hormones influence nicotine metabolism. Nicotine and cotinine metabolism is faster in women than in men and is faster in women taking oral contraceptives compared with those who are not. Accelerated nicotine metabolism appears to be a result of estrogen. Sex-related differences in nicotine clearance could affect smoking behaviors, as well as response to nicotine medications, and could be a marker for altered metabolism of nicotine-derived carcinogens.