女性性别及口服避孕药的使用会加速尼古丁代谢。

Female sex and oral contraceptive use accelerate nicotine metabolism.

作者信息

Benowitz Neal L, Lessov-Schlaggar Christina N, Swan Gary E, Jacob Peyton

机构信息

Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, University of California, San Francisco, San Francisco 94143-1220, USA.

出版信息

Clin Pharmacol Ther. 2006 May;79(5):480-8. doi: 10.1016/j.clpt.2006.01.008.

DOI:10.1016/j.clpt.2006.01.008

PMID:16678549

Abstract

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.

摘要

背景

多项研究报告称，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及相关吸烟行为的性别差异有关。本研究检验了以下假设：女性代谢尼古丁的速度比男性快，且在女性中，口服避孕药使用者代谢尼古丁的速度比未使用口服避孕药者快。

方法

从北加利福尼亚双胞胎登记处招募了278名健康的双胞胎志愿者以及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静脉输注，并频繁采集血样。测量了尼古丁和可替宁的血浆清除率、尼古丁向可替宁的清除率（细胞色素P450 [CYP] 2A6活性指标）以及反式-3'-羟基可替宁与可替宁的比值（CYP2A6活性的另一个指标）。

结果

女性的尼古丁和可替宁清除率、尼古丁向可替宁的清除率以及反式-3'-羟基可替宁/可替宁比值均显著高于男性（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）；在服用口服避孕药的女性中，这些指标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，未服用者为17.6±6.1 mL·min⁻¹·kg⁻¹；P <.05）。绝经或绝经后的女性与男性无差异。在口服避孕药使用者中，服用复方和仅含雌激素避孕药的女性尼古丁代谢加快，但仅服用孕激素避孕药的女性未出现这种情况。