Evaluation of the Effect of Ammonia on Nicotine Pharmacokinetics Using Rapid Arterial Sampling

Introduction: The nicotine bolus theory states that the dependence-producing potential of cigarettes relates to a rapid increase in nicotine at brain receptor sites. It has been suggested that ammonia, a compound typically found in tobacco products, further increases the amount of nicotine absorbed and its absorption rate. The aim of this study was to determine whether different ammonia yields in cigarettes affected the rate or amount of nicotine absorption from the lungs to arterial circulation. Methods: 34 adult smokers received 3 separate puffs from each of 2 test cigarettes with different ammonia yields (ammonia in smoke: 10.1 mg per cigarette vs. 18.9 mg per cigarette), followed by rapid radial arterial blood sampling (maximum one sample per second) with 30 min between puffs. Arterial blood samples were assayed for nicotine by liquid chromatography tandem mass spectrometry. Pharmacokinetic modeling was performed and the two test cigarettes were assessed for bioequivalence. Results: No significant differences were found in area under the curve, C max , or T max and the 2 test cigarettes were found to be bioequivalent based on 2 one-sided tests at a significance level of 5%. In addition, the zero-order rate constant (k 0 ) obtained from the initial slope of the curves and the model-dependent first-or der rate constant (k a ) were not significantly different. Conclusions: This study provides strong evidence that the different ammonia yields of the test cigarettes had no impact on nicotine pharmacokinetics; thus, the ammonia did not increase the rate or amount of nicotine absorption from a puff of cigarette smoke.