Accelerated metabolism of nicotine and cotinine in pregnant smokers
Accelerated metabolism of nicotine and cotinine in pregnant smokers
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DOI：
10.1124/jpet.301.2.594
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发表时间：
2002-05-01
影响因子：
3.5
通讯作者：
Benowitz, NL
中科院分区：
文献类型：
--
作者：
Dempsey, D;Jacob, P;Benowitz, NL
吸烟是不良妊娠结局的最重要的可改变的风险因素。尼古丁是一种可疑的胎儿神经致畸剂。人们担心，如果尼古丁替代疗法的处方剂量为非妊娠状态下使用的剂量，则尼古丁可能在妊娠期间达到毒性水平。10名健康的志愿者，怀孕吸烟者在怀孕期间和产后接受了氘标记的尼古丁和可替宁的输注。根据血液和尿液测量结果，确定以下内容：尼古丁和可替宁的清除率（肾脏和非肾脏）、尼古丁通过可替宁途径的清除率（CYP 2A 6活性的一个指标）以及吸烟引起的尼古丁每日摄入量。在妊娠期间，尼古丁和可替宁的清除率显著较高（分别为60%和140%），可替宁的半衰期短得多（8.8 vs 16.6 h，P < 0.01）。虽然怀孕期间血浆可替宁水平较低（119与202 ng/ml，P < 0.05），但怀孕期间和产后吸烟引起的每日尼古丁摄入量相似。对于给定的摄入水平，预计妊娠期间尼古丁的药理学和毒理学效应低于非妊娠女性尼古丁代谢数据的预期。我们的数据表明，在妊娠期间无需对尼古丁替代疗法进行剂量下调。相反，可能需要高于正常剂量的尼古丁来优化疗效。在怀孕期间观察到的较低的可替宁水平并不一定反映较少的烟雾暴露，并且需要为怀孕确定用于分类非吸烟者，被动吸烟者和主动吸烟者的截止水平。
Cigarette smoking is the foremost modifiable risk factor for adverse pregnancy outcomes. Nicotine is a suspected fetal neuroteratogen. There is concern that nicotine may achieve toxic levels during pregnancy if nicotine replacement therapies are prescribed at doses used in the nonpregnant state. Ten healthy, volunteer, pregnant smokers received infusions of deuterium-labeled nicotine and cotinine during pregnancy and again postpartum. From blood and urine measurements, the following were determined: clearance (renal and nonrenal) of nicotine and cotinine, clearance of nicotine via the cotinine pathway (an indicator of CYP2A6 activity), and daily intake of nicotine from smoking. The clearance of nicotine and cotinine was significantly higher (60 and 140%, respectively), and the half-life of cotinine was much shorter (8.8 versus 16.6 h, P < 0.01) during pregnancy. Although plasma levels of cotinine were lower during pregnancy (119 versus 202 ng/ml, P < 0.05), daily intake of nicotine from smoking was similar during pregnancy and postpartum. For a given level of intake, the pharmacologic and toxicologic effects of nicotine during pregnancy are anticipated to be less than expected from nicotine metabolism data in nonpregnant women. Our data indicate that no downward dose adjustment needs to be made for nicotine replacement therapy during pregnancy. Conversely, higher than usual doses of nicotine may be necessary to optimize efficacy. Lower cotinine levels observed during pregnancy do not necessarily reflect less smoke exposure, and cut-off levels used to classify nonsmokers, passive smokers, and active smokers need to be established for pregnancy.