McGovren J P, Lubawy W C, Kostenbauder H B
J Pharmacol Exp Ther. 1976 Oct;199(1):198-207.
In order to investigate the possibility of pulmonary first-pass metabolism of nicotine inhaled in tobacco smoke, the absorption and disposition of 14C-nicotine were studied in an isolated perfused rabbit lung preparation after nicotine administration directly into the perfusing blood and tobacco smoke administration via in the inspired tracheal air. After administration into the perfusing medium, the rate of nicotine metabolism was first-order and dose-independent at the two doses studies (0.1 and 1.0 mg) but lung metabolic clearance was quite low (3 ml/min) relative to whole body clearance (140 ml/min) measured by administering 14C-nicotine to intact rabbits. Accumulation of nicotine by lung was not extensive (13-23% of the dose administered). After administration of tobacco smoke from 14C-nicotine-spiked cigarettes, absorption of nicotine was rapid but the rate of metabolism was markedly reduced compared to the studies in which drug was administered in the perfusing medium. This reduction in the rate of metabolism was apparently caused by some component of tobacco smoke but was shown to be unrelated to the level of carbon monoxide in the perfusate. The slow clearance of nicotine by rabbit lung (which is further reduced after smoke administration) compared to a high pulmonary blood flow rate makes unlikely the possibility of significant first-pass lung metabolism in smokers.
为了研究烟草烟雾中吸入的尼古丁的肺首过代谢可能性，在将尼古丁直接注入灌注血液以及通过吸入气管空气给予烟草烟雾后，在离体灌注兔肺制备物中研究了14C-尼古丁的吸收和处置。注入灌注介质后，在两项剂量研究（0.1和1.0毫克）中，尼古丁代谢速率呈一级且与剂量无关，但相对于通过向完整兔给予14C-尼古丁测得的全身清除率（140毫升/分钟），肺代谢清除率相当低（3毫升/分钟）。肺对尼古丁的蓄积并不广泛（占给药剂量的13%-23%）。给予含14C-尼古丁的香烟产生的烟草烟雾后，尼古丁吸收迅速，但与在灌注介质中给药的研究相比，代谢速率明显降低。代谢速率的这种降低显然是由烟草烟雾的某些成分引起的，但已证明与灌注液中一氧化碳的水平无关。与高肺血流量相比，兔肺对尼古丁的清除缓慢（烟雾给药后进一步降低），这使得吸烟者肺首过代谢显著的可能性不大。
