CLINICAL PHARMACOKINETICS OF NASAL NICOTINE DELIVERY - A REVIEW AND COMPARISON TO OTHER NICOTINE SYSTEMS

Rapid drug delivery (arterial 'boli') and high drug concentrations occ ur with nicotine inhaled in smoke, These are believed to be key elemen ts in producing addiction to cigarettes, Preparations which reduce the rate of delivery and/or concentration of nicotine have been introduce d 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 expecte d to affect efficacy and treatment dependence, Nasal administration sy stems have been developed to more closely approximate cigarette delive ry for improved efficacy in clinical application and for more control in systematic testing of nicotine. With laboratory tested nasal applic ation systems (clinical drug and experimental devices), venous plasma concentrations after a single dose range between 5 and 12 mu g/L. High er steady-state blood nicotine concentrations (16 to 29 mu g/L) have b een reported for ad libitum clinical self-administration with a nicoti ne nasal spray. Time to peak plasma concentration (t(max) with nasal a dministration is around 11 to 13 minutes for 1 mg doses. This rise tim e is slower than for cigarette delivery but faster than the other nico tine treatments. Venous plasma concentrations are considerably lower t han tobacco product concentrations and fall within the range of the lo wer dose nicotine treatments (e.g. 2mg gum vs 4mg gum). The profile of nasal nicotine administration was designed for certain subsets of smo kers. Efficacy trials show consistent superiority of nasal administrat ion over placebo although the comparative efficacy among nicotine trea tments remains to be determined. The more rapid onset and user control of nasal nicotine may impose a higher risk for treatment dependence c ompared with a slower, passive system such as the patch. It may not pr oduce more dependence than other faster-acting treatment systems (e.g. nicotine gum).