Gourlay S G, Benowitz N L
Division of Clinical Pharmacology and Experimental Therapeutics, San Francisco General Hospital Medical Center, CA, USA.
Clin Pharmacol Ther. 1997 Oct;62(4):453-63. doi: 10.1016/S0009-9236(97)90124-7.
Delivery of a high concentration bolus of nicotine through the arterial circulation is believed to be an important determinant of the addictive, behavioral, and physiologic effects of nicotine. To better understand the pharmacologic features of nicotine with different routes of administration, we measured arterial and venous plasma concentrations of nicotine, cotinine, epinephrine, and norepinephrine after tobacco smoking, intravenous nicotine infusion, and use of a nicotine nasal spray.
Arterial and venous blood samples were drawn simultaneously from 12 male smokers. Six subjects received a single dose of 1 mg nicotine nasal spray, and six subjects smoked cigarettes, one puff per minute for 10 minutes. All 12 subjects were administered nicotine as a 30-minute infusion beginning 70 minutes after administration of the nicotine nasal spray or commencement of smoking.
The mean peak arterial plasma concentrations of nicotine (Cmax) after smoking or administration of nicotine nasal spray, or intravenous nicotine averaged twofold those of venous plasma. For nicotine nasal spray, the time to Cmax was much faster for arterial than for venous plasma (median, 5 versus 18 minutes, p < 0.01). Intravenous nicotine produced the greatest increase in plasma epinephrine concentration, although smoking had a greater chronotropic effect. Acute tolerance to the chronotropic effects of nicotine was suggested at pharmacodynamic analysis with venous nicotine concentrations, whereas analysis of arterial concentrations found the opposite--a time lag between plasma concentration and effect.
Nicotine is rapidly absorbed from nicotine nasal spray. The Cmax of nicotine after smoking or administration of nicotine nasal spray, or intravenous nicotine is substantially higher in arterial than venous plasma. Acute tolerance to the chronotropic effects of nicotine is not apparent if arterial plasma concentrations are measured.
经动脉循环递送高浓度尼古丁推注被认为是尼古丁成瘾、行为及生理效应的重要决定因素。为更好地了解不同给药途径尼古丁的药理学特征，我们测量了吸烟、静脉输注尼古丁及使用尼古丁鼻喷雾剂后动脉和静脉血浆中尼古丁、可替宁、肾上腺素和去甲肾上腺素的浓度。
同时从12名男性吸烟者采集动脉和静脉血样。6名受试者接受单剂量1mg尼古丁鼻喷雾剂，6名受试者吸烟，每分钟吸一口，共吸10分钟。所有12名受试者在给予尼古丁鼻喷雾剂或开始吸烟70分钟后开始进行30分钟的尼古丁静脉输注。
吸烟、给予尼古丁鼻喷雾剂或静脉输注尼古丁后，尼古丁的平均动脉血浆峰浓度（Cmax）平均为静脉血浆的两倍。对于尼古丁鼻喷雾剂，动脉血浆达到Cmax的时间比静脉血浆快得多（中位数分别为5分钟和18分钟，p<0.01）。静脉输注尼古丁使血浆肾上腺素浓度升高幅度最大，尽管吸烟对心率的影响更大。在对静脉尼古丁浓度进行药效学分析时提示对尼古丁的变时效应存在急性耐受性，而对动脉浓度分析时结果相反——血浆浓度与效应之间存在时间滞后。
尼古丁鼻喷雾剂中尼古丁吸收迅速。吸烟、给予尼古丁鼻喷雾剂或静脉输注尼古丁后，动脉血浆中尼古丁的Cmax显著高于静脉血浆。如果测量动脉血浆浓度，对尼古丁变时效应的急性耐受性并不明显。
