Clinical pharmacokinetics of nasal nicotine delivery. A review and comparison to other nicotine systems.

Rapid drug delivery (arterial "boli') and high drug concentrations occur with nicotine inhaled in smoke. These are believed to be key elements in producing addiction to cigarettes. Preparations which reduce the rate of delivery and/or concentration of nicotine have been introduced as treatments for smoking cessation. These nicotine medications work by relieving withdrawal and preventing relapse associated with abrupt cessation of smoking. The pharmacokinetics of each system are expected to affect efficacy and treatment dependence. Nasal administration systems have been developed to more closely approximate cigarette delivery for improved efficacy in clinical application and for more control in systematic testing of nicotine. With laboratory tested nasal application systems (clinical drug and experimental devices), venous plasma concentrations after a single dose range between 5 and 12 micrograms/L. Higher steady-state blood nicotine concentrations (16 to 29 micrograms/L) have been reported for ad libitum clinical self-administration with a nicotine nasal spray. Time to peak plasma concentration (tmax) with nasal administration is around 11 to 13 minutes for 1 mg doses. This rise time is slower than for cigarette delivery but faster than the other nicotine treatments. Venous plasma concentrations are considerably lower than tobacco product concentrations and fall within the range of the lower dose nicotine treatments (e.g. 2 mg gum vs 4 mg gum). The profile of nasal nicotine administration was designed for certain subsets of smokers. Efficacy trials show consistent superiority of nasal administration over placebo although the comparative efficacy among nicotine treatments remains to be determined. The more rapid onset and user control of nasal nicotine may impose a higher risk for treatment dependence compared with a slower, passive system such as the patch. It may not produce more dependence than other faster-acting treatment systems (e.g. nicotine gum).