Pharmacokinetic considerations in understanding nicotine dependence.

The pharmacokinetic and pharmacodynamic characteristics of a drug are important determinants of whether users become dependent on it and of the temporal patterns of drug use. Characteristics of cigarette smoking, which produces a high degree of dependence, and the use of nicotine gum, which has a relatively low risk of dependence, are compared. Nicotine from tobacco smoke is rapidly absorbed and transferred into the brain. This results in high brain concentrations and intensive psychological effects, with relatively little development of tolerance. The smoker may titrate the level of drug and associated psychological effects of nicotine. Thus, smoking provides a nearly optimal situation for behavioural reinforcement. Chewing nicotine gum results in slow absorption of nicotine, leading to lower levels of nicotine in the brain and substantial time for development of tolerance. Thus, the intensity of effect is less and the onset of effect is delayed from the onset of dosing, providing less opportunity for behavioural reinforcement. Pharmacokinetic and pharmacodynamic modelling techniques have been applied to these processes and used to assess the implications for understanding the daily smoking cycle.