In vivo human buccal permeability of nicotine

The aim was to examine the in vivo buccal pH-dependent permeability of nicotine in humans and furthermore compare the in vivo permeability of nicotine to previous in vitro permeability data. The buccal permeability of nicotine was examined in a three-way cross-over study in eight healthy non-smokers using a buccal perfusion cell. The disappearance of nicotine from perfusion solutions with pH 6.0, 7.4, and 8.1 was studied for 3 h. The apparent permeability of nicotine (Papp) was determined at each pH value. Parotid saliva was collected in an attempt to assess systemic levels of nicotine. The disappearance rate of nicotine increased significantly as the pH increased, which resulted in Papp values of 0.57 ± 0.55 × 10−4, 2.10 ± 0.23 × 10−4, and 3.96 ± 0.54 × 10−4 cm s−1 (mean ± S.D.) at pH 6.0, 7.4, and 8.1, respectively. A linear relationship (R2 = 0.993) was obtained between the Papp values and non-ionised nicotine, which indicates that the nicotine transfer occurred by means of passive diffusion. Papp values of 0.60 × 10−4 and 6.18 × 10−4 cm s−1 were obtained for the mono-protonated and non-ionised species of nicotine, respectively. The analysis of the parotid saliva samples indicated that these samples might be useful in the assessment of systemic absorption of nicotine. Previous buccal in vitro models underestimated the in vivo human permeability of nicotine. However, the in vitro models were capable of predicting the effect of pH on the nicotine permeability.