The nicotine inhaler - Clinical pharmacokinetics and comparison with othernicotine treatments

Nicotine inhaled in smoke is the most rapid form of delivery of the drug. W ith smoking, arterial boli and high venous blood nicotine concentrations ar e produced within seconds and minutes. respectively. The potency of nicotin e as the primary reinforcement in tobacco addiction is attributed to this r apid rate of delivery. By design, nicotine treatments reduce the rate and e xtent of drug delivery for weaning from nicotine during smoking cessation. Theoretically, they prevent relapse by reducing withdrawal and craving asso ciated with the abrupt cessation of cigarettes. The nicotine inhaler treats the complexity of smoking through weaning both from the drug and from the sensory/ritual components associated with smokin g. The inhaler is 'puffed' but not lit and there is considerable 'puffing' required to achieve slower rising and lower nicotine concentrations. These factors allow it to be used as a nicotine reduction treatment. One inhaler contains 10mg of nicotine (and 1mg of menthol) of which 4mg of nicotine can be extracted and 2mg are systemically available. Shallow or de ep 'puffing' results in similar nicotine absorption. Nicotine is delivered mainly to the oral cavity, throat and upper respiratory tract with a minor fraction reaching the lungs. This was confirmed with positron emission tomo graphy and by assessment of arterial concentrations. A single inhaler can b e used for one 20-minute period of continuous puffing or periodic use of up to 400 puffs per inhaler. With controlled puffing in laboratory testing, venous plasma nicotine conce ntrations from a single inhaler puffed 80 times over 20 minutes averaged 8. 1 mug/L at 30 minutes. Lower concentrations of 6.4 to 6.9 mug/L have been r eported for self-administration under clinical conditions. The time to peak plasma concentrations varies but is always significantly longer than with cigarette delivery. Estimates of nicotine intake from cotinine concentratio ns were higher than expected (60 to 70% of baseline smoking concentrations) . This elevation may be due to the swallowing of nicotine and subsequent fi rst-pass biotransformation to cotinine. In general. venous blood nicotine c oncentrations are considerably lower than with smoking and are within the r ange observed for other nicotine reduction therapies. Efficacy trials show consistent superiority of the inhaler over placebo. De spite the 'cigarette-like' appearance of the inhaler and the associated sen sory/ritual elements. little treatment dependence or abuse has been reporte d. This is attributed to the slow rise time and low nicotine blood concentr ations. The inhaler is a valuable addition to treatment of tobacco dependen ce and can be used alone or with other treatments.