Various formulations of nicotine replacement therapy (NRT), such as nicotine gum, transdermal patch, nasal spray, inhaler, sublingual tablets, and lozenges, are buffered to alkaline pH to facilitate absorption of nicotine through cell membranes. Absorption of nicotine from all NRTs is slower and the increase in nicotine blood levels is more gradual than from smoking. This slow increase in blood and especially in brain levels results in low abuse liability of NRTs (West et al. 2000). Only nasal spray provides a rapid delivery of nicotine that is closer to the rate of nicotine delivery achieved with smoking (Gourlay and Benowitz 1997; Guthrie et al. 1999). The absolute dose of nicotine absorbed systemically from nicotine gum is much less than the nicotine content of the gum, in part, because considerable nicotine is swallowed with subsequent first-pass metabolism (Benowitz et al. 1987). Some nicotine is also retained in chewed gum. A portion of the nicotine dose is swallowed and subjected to first-pass metabolism when using other NRTs, inhaler, sublingual tablets, nasal spray, and lozenges. Bioavailability for these products with absorption mainly through the mucosa of the oral cavity and a considerable swallowed portion is about 50–80%.