Regional deposition of inhaled 11C-nicotine vapor in the human airway as visualized by positron emission tomography*

Abstract

The deposition of 11C-nicotine in the respiratory tract from a nicotine vapor inhaler was studied by means of positron emission tomography (PET) in an intrasubject comparison of six healthy smokers using two modes of inhalation: one with shallow, frequent inhalations ("buccal mode") and one with deep inhalations ("pulmonary mode"). An average of 15% of the radioactivity was released from the vapor inhaler after 5 minutes of inhalation. Approximately 45% of the dose released was found in the oral cavity. A significant amount of radioactivity, 10%, was observed in the esophagus, suggesting transfer of a major fraction of the dose to the stomach. Only a minor fraction, 5%, was found in the lungs, followed by 2% in the bronchi and 1% in the trachea. The deposition in the oral cavity closely followed a linear pattern during the 5 minutes of inhalation and was followed by a rapid elimination from the oral cavity, with an average half-life of 18 minutes. Only 8% of the dose released remained in the oral cavity 45 minutes after the end of inhalation. On the other hand, the dose fraction of about 14% distributed into the body tissue compartment at the end of inhalation had risen to 60% at that late time point. No statistically or clinically important differences were observed between the buccal and the pulmonary mode of inhalation in either deposition pattern or elimination rates.

Effect of nicotine vapour inhalation on the relief of tobacco withdrawal symptoms

“…Testing a similar device, Favor ®, with the pulmonary technique they stated that their results suggested that the major route of absorption was buccal rather than pulmonary. In one study, using Positron Emission Tomography (PET) (Bergstr6m et al 1995) to investigate the deposition of nicotine in the airways after use of a vapour inhaler, approximately 45 % of the dose was recovered in the oral cavity, while less than 5 % was found in the lungs, irrespective of mode of inhalation. One interesting aspect of this is the possible difference in abuse liability between various preparations related to their nicotine delivery kinetics, as discussed by Henningfield and Keenan (1993).…”

Smoking produces rapid rise of [11C]nicotine in human brain

“…There is some anecdotal support for the hypothesis that smoked drugs are generally more abused than other forms, and it has been posited that smoking cigarettes produces a particularly rapid rate of rise of nicotine in the brain (Henningfield et al , 2000Henningfield and Keenan 1993;Rose et al 1999Rose et al , 2007Stitzer and de Wit 1998). Conventional nicotine pharmacokinetics have been measured (Gourlay and Benowitz 1997;Henningfield and Keenan 1993;Rose et al 1999;Spencer et al 2006) and so have brain kinetics after intravenous delivery of [ 11 C]nicotine (Muzic et al 1998;Nordberg et al 1989Nordberg et al , 1990Nordberg et al , 1995Nybäck et al 1994), after inhalation with a vapor inhaler (Bergstrom et al 1995;Lunell et al 1996) and after nasal administration (Schneider et al 1996). However, data for kinetics and rate of rise in brain tissue after smoked nicotine delivery are lacking and may be different from data previously measured following other methods of administration.…”

Metabolism and Disposition Kinetics of Nicotine

“…NICOTINE METABOLISM pass metabolism when using other NRTs, inhaler, sublingual tablets, nasal spray, and lozenges (Johansson et al, 1991;Bergstrom et al, 1995;Lunell et al, 1996;Choi et al, 2003). Bioavailability for these products with absorption mainly through the mucosa of the oral cavity and a considerable swallowed portion is about 50 to 80% (Table 1).…”