Ng. Schneider et al., CLINICAL PHARMACOKINETICS OF NASAL NICOTINE DELIVERY - A REVIEW AND COMPARISON TO OTHER NICOTINE SYSTEMS, Clinical pharmacokinetics, 31(1), 1996, pp. 65-80
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).