Nicotine intake is considered to be a major factor in sustaining tobacco addiction. For this reason, nicotine gum has recently been introduced as an adjuvant to smoking cessation. The introduction of nicotine as a ‘therapeutic’ entity necessitates a careful examination of its clinical pharmacokinetics.Insufficient data exist to quantitatively assess the absorption of nicotine after oral administration. Based upon physicochemical and pharmacokinetic principles, the oral bioavailability of nicotine would be expected to be less than 20%. The limited data available in the literature appear to support this conclusion. Absorption from the oral mucosa is the principal site of nicotine absorption in subjects who chew tobacco or nicotine gum. Absorption by this route is highly pH dependent. Nicotine is also readily absorbed from the nasal mucosa, and after topical administration.Nicotine distributes extensively into body tissues with a volume of distribution ranging from 1.0 to 3.0 L/kg. Nicotine has been shown to transfer across the placenta and into breast milk in humans. Plasma protein binding is negligible, ranging from 4.9 to 20%.The predominant route of nicotine elimination is hepatic metabolism. Although a number of metabolites of nicotine have been identified, it is unclear whether any of these compounds contribute to the pharmacological effect of nicotine. Nicotine is also excreted unchanged in urine in a pH-dependent fashion. With urinary pH less than 5, an average 23% of the nicotine dose is excreted unchanged. When urinary pH is maintained above 7.0, unchanged nicotine urinary excretion drops to 2%.After intravenous administration, nicotine exhibits biexponential decline in plasma. Total plasma clearance ranges from 0.92 to 2.43 L/min. During urinary acidification, renal clearance averages 0.20 L/min. Non-renal blood clearance averages 1.2 L/min, indicating that nicotine elimination is dependent on hepatic blood flow.The literature is devoid of information regarding the effect of disease on the pharmacokinetics of nicotine. Based upon the drug's pharmacokinetics in healthy smokers, it would be anticipated that disease states which alter hepatic blood flow may have the greatest impact on nicotine pharmacokinetics. In addition, drugs which alter hepatic blood flow may cause significant alterations in the systemic clearance of nicotine.Dependence on smoking appears to be related, at least in part, to the achievement of a rapid rise in plasma nicotine concentrations. If this assessment is correct, the most desirable adjuvant for smoking cessation would be one that closely mimics this pattern of plasma nicotine concentrations. Thus, the slow rise in plasma concentrations after chewing nicotine gum may suggest a pharmacokinetic explanation for the relatively high failure rate with this method of smoking cessation. It appears that because the rate of nicotine absorption is even slower than with the gum formulation, transdermal preparations are unlikely to be a satisfactory alternative to smoking. Further investigations are, therefore, required to determine a formulation which gives the desired plasma nicotine concentration profile.One of the major effects of smoking on drug therapy is the induction of drug-metabolising enzymes. However, the effects on drug metabolising capacity when a subject changes from smoking to nicotine gum has not yet been studied. The effect nicotine itself has on drug metabolism in humans is also unknown.Considerable work remains to define adequately the clinical pharmacokinetics of nicotine. Determination of factors which influence the efficacy of nicotine as an adjuvant in smoking cessation may prove beneficial in reducing the number of tobacco consumers worldwide.