Department of Internal Medicine, University of Oulu, Oulu, Finland.
Br J Clin Pharmacol. 2010 Feb;69(2):152-9. doi: 10.1111/j.1365-2125.2009.03568.x.
Smoking slows the metabolism of nicotine and accelerates the metabolism of chlorzoxazone, which are probe reactions for cytochrome P450 2A6 (CYP2A6) and CYP2E1 activities, respectively. We aimed to determine the role of nicotine in these metabolic effects of cigarette smoking.
The study had a single-blind, randomized, crossover two-arm design. Twelve healthy smokers were given two transdermal patches with 42-mg nicotine a day or placebo patches, each for 10 days. The subjects abstained from smoking during the study arms. Oral chlorzoxazone was given on day 7 and deuterium-labelled nicotine-d(2) and cotinine-d(4) infusion on day 8.
There was no significant influence of transdermal nicotine administration on pharmacokinetic parameters of nicotine-d(2) or on the formation of cotinine-d(2). Nicotine decreased the volume of distribution (62.6 vs. 67.7 l, 95% confidence interval of the difference -9.7, -0.6, P= 0.047) of infused cotinine-d(4). There were no significant differences in disposition kinetics of chlorzoxazone between the treatments.
CYP2A6 and CYP2E1 activities are not affected by nicotine. The tobacco smoke constituents responsible for the reduced CYP2A6 and increased CYP2E1 activities remain unknown.
吸烟会减缓尼古丁的代谢速度，并加速氯唑沙宗的代谢速度，后者分别是细胞色素 P450 2A6（CYP2A6）和 CYP2E1 活性的探针反应。我们旨在确定尼古丁在吸烟引起的这些代谢效应中的作用。
本研究采用单盲、随机、交叉双臂设计。12 名健康吸烟者每天接受两片 42 毫克尼古丁贴片或安慰剂贴片，各 10 天。在研究臂期间，受试者禁止吸烟。第 7 天给予口服氯唑沙宗，第 8 天给予氘标记尼古丁-d（2）和可替宁-d（4）输注。
经皮尼古丁给药对尼古丁-d（2）的药代动力学参数或可替宁-d（2）的形成没有显著影响。尼古丁降低了输注可替宁-d（4）的分布容积（62.6 与 67.7 l，差异的 95%置信区间为-9.7，-0.6，P=0.047）。两种治疗方法之间氯唑沙宗的处置动力学无显著差异。
CYP2A6 和 CYP2E1 活性不受尼古丁影响。导致 CYP2A6 活性降低和 CYP2E1 活性增加的烟草烟雾成分仍不清楚。
