Benowitz N L, Jacob P, Denaro C, Jenkins R
Department of Medicine, University of California, San Francisco.
Clin Pharmacol Ther. 1991 Mar;49(3):270-7. doi: 10.1038/clpt.1991.28.
The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine.
使用稳定同位素标记的化合物3',3'-双氘代尼古丁来研究吸烟者体内尼古丁的处置动力学、香烟烟雾中尼古丁的全身吸收以及口服胶囊摄入尼古丁的生物利用度。在30分钟静脉输注后，可在9小时内测量标记尼古丁的血药浓度。对10名健康男性的处置动力学分析显示，输注结束后呈多指数下降，消除半衰期平均为203分钟。该半衰期比先前报道的更长，表明存在一个缓慢的消除阶段。血浆清除率平均为14.6 ml/min/kg。每支香烟的尼古丁平均摄入量为2.29 mg。在这些受试者中评估了一种直接测量烟雾中颗粒物的香烟烟雾监测系统。总颗粒物、香烟抽吸次数、总抽吸量和抽吸时间与吸烟时尼古丁的摄入量相关。尼古丁的口服生物利用度平均为44%。该生物利用度高于基于尼古丁全身清除率的预期值，表明尼古丁可能存在显著的肝外代谢。
