Adrian Charlotte L, Olin Helle B D, Dalhoff Kim, Jacobsen Jette
The Danish University of Pharmaceutical Sciences, Department of Pharmaceutics, Universitetsparken 2, Copenhagen, Denmark.
Int J Pharm. 2006 Mar 27;311(1-2):196-202. doi: 10.1016/j.ijpharm.2005.12.039. Epub 2006 Feb 7.
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 3h. The apparent permeability of nicotine (P(app)) 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 P(app) values of 0.57+/-0.55 x 10(-4), 2.10+/-0.23 x 10(-4), and 3.96+/-0.54 x 10(-4)cms(-1) (mean+/-S.D.) at pH 6.0, 7.4, and 8.1, respectively. A linear relationship (R(2)=0.993) was obtained between the P(app) values and non-ionised nicotine, which indicates that the nicotine transfer occurred by means of passive diffusion. P(app) values of 0.60 x 10(-4) and 6.18 x 10(-4)cms(-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.
本研究旨在考察尼古丁在人体口腔内的pH依赖性体内渗透性，并将尼古丁的体内渗透性与先前的体外渗透性数据进行比较。在一项三交叉研究中，使用口腔灌注池对8名健康非吸烟者的尼古丁口腔渗透性进行了检测。研究了pH值分别为6.0、7.4和8.1的灌注溶液中尼古丁3小时内的消失情况。测定了每个pH值下尼古丁的表观渗透率（P(app)）。收集腮腺唾液以评估尼古丁的全身水平。随着pH值升高，尼古丁的消失速率显著增加，导致pH值为6.0、7.4和8.1时的P(app)值分别为0.57±0.55×10(-4)、2.10±0.23×10(-4)和3.96±0.54×10(-4) cm s(-1)（平均值±标准差）。P(app)值与非离子化尼古丁之间呈线性关系（R(2)=0.993），这表明尼古丁的转运是通过被动扩散进行的。尼古丁单质子化和非离子化形式的P(app)值分别为0.60×10(-4)和6.18×10(-4) cm s(-1)。腮腺唾液样本分析表明，这些样本可能有助于评估尼古丁的全身吸收情况。先前的口腔体外模型低估了尼古丁在人体的体内渗透性。然而，体外模型能够预测pH值对尼古丁渗透性的影响。
