薄荷醇对吸烟大鼠体内尼古丁药代动力学的影响。
Effect of menthol on nicotine pharmacokinetics in rats after cigarette smoke inhalation.
机构信息
Department of Pharmaceutical Sciences, Texas Southern University, Houston, TX 77004, USA.
出版信息
Nicotine Tob Res. 2012 Jul;14(7):801-8. doi: 10.1093/ntr/ntr287. Epub 2012 Feb 6.
INTRODUCTION
The effect of menthol on nicotine disposition is important in understanding smoking behaviors among different racial groups. The present study was to evaluate whether menthol affects the pharmacokinetics of nicotine after cigarette smoke inhalation.
METHODS
Rats were exposed to mainstream smoke from either a nonmentholated or mentholated cigarette (1 puff/min for 10 min) using a smoke inhalation apparatus. For the multiple-cigarette smoke inhalation, rats received the smoke from either nonmentholated or mentholated cigarette (10 puffs) every 12 hr for a total of 17 cigarettes. Serial blood samples were collected during the 10-min inhalation phase for the single-cigarette smoke or the 17th cigarette inhalation and for 30 hr thereafter. Nicotine and its major metabolite cotinine were assayed by radioimmunoassay methods.
RESULTS
Following single-cigarette smoke inhalation, mentholated cigarettes significantly decreased the mean peak concentrations of nicotine in plasma (C(max)) from 27.1 to 9.61 ng/ml and the total area under the plasma concentration-time curves (AUC) from 977 to 391 ng min/ml as compared with those after nonmentholated cigarette smoke inhalation. C(max) and AUC values for cotinine were also significantly reduced by menthol. Similarly after multiple smoke inhalation, C(max), AUC, and the mean average steady-state plasma concentration of nicotine as well as cotinine were significantly lower in mentholated cigarette inhalation. Interestingly, there was a significant increase in the cotinine to nicotine AUC ratio from 13.8 for the nonmentholated to 21.1 for the mentholated cigarette.
CONCLUSIONS
These results suggest that menthol in mentholated cigarettes can substantially decrease the absorption and/or increase the clearance of nicotine.
简介
薄荷醇对尼古丁分布的影响对于理解不同种族群体的吸烟行为很重要。本研究旨在评估薄荷醇是否会影响吸烟后尼古丁的药代动力学。
方法
使用烟雾吸入装置，使大鼠暴露于非薄荷醇或薄荷醇香烟的主流烟雾中（1 口/分钟，持续 10 分钟）。对于多次吸烟，大鼠每 12 小时接受非薄荷醇或薄荷醇香烟的烟雾（10 口），总共吸入 17 支香烟。在单次吸烟或第 17 支吸烟的 10 分钟吸入期间和之后的 30 小时内采集连续的血液样本。采用放射免疫测定法测定尼古丁及其主要代谢物可替宁的浓度。
结果
与非薄荷醇香烟烟雾吸入后相比，在单次吸烟后，薄荷醇香烟使血浆中尼古丁的平均峰值浓度（Cmax）从 27.1 降至 9.61ng/ml，总血浆浓度-时间曲线下面积（AUC）从 977 降至 391ng min/ml。可替宁的 Cmax 和 AUC 值也明显降低。同样，在多次吸烟后，薄荷醇香烟吸入的 Cmax、AUC、尼古丁的平均稳态血浆浓度以及可替宁均显著降低。有趣的是，非薄荷醇香烟的可替宁与尼古丁 AUC 比值为 13.8，而薄荷醇香烟的比值为 21.1，这一比值显著增加。
结论
这些结果表明，薄荷醇可以显著降低薄荷醇香烟中尼古丁的吸收和/或增加其清除率。
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