Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
McNeil AB, Helsingborg, Sweden.
Clin Pharmacol Ther. 2020 Jan;107(1):238-245. doi: 10.1002/cpt.1595. Epub 2019 Sep 3.
Tobacco use is a major health concern. To assist smoking cessation, nicotine replacement therapy (NRT) is used to reduce nicotine craving. We quantitatively described the relationship between nicotine pharmacokinetics (PKs) from NRTs and momentary craving, linking two different pharmacodynamic (PD) scales for measuring craving. The dataset comprised retrospective data from 17 clinical studies and included 1,077 adult smokers with 39,802 craving observations from four formulations: lozenge, gum, mouth spray, and patch. A PK/PD model was developed that linked individual predicted nicotine concentrations with the categorical and visual analogue PD scales through a joint bounded integer model. A maximum effect model, accounting for acute tolerance development, successfully related nicotine concentrations to momentary craving. Results showed that all formulations were similarly effective in reducing craving, albeit with a fourfold lower potency for the patch. Women were found to have a higher maximal effect of nicotine to reduce craving, compared with men.
吸烟是一个主要的健康关注点。为了帮助戒烟，尼古丁替代疗法（NRT）被用于减少尼古丁渴望。我们定量描述了 NRT 中的尼古丁药代动力学（PKs）与即时渴望之间的关系，将两种不同的测量渴望的药效学（PD）量表联系起来。该数据集包含来自 17 项临床研究的回顾性数据，包括 1077 名成年吸烟者，有来自四种制剂（含片、口香糖、口腔喷雾和贴片）的 39802 次渴望观察。通过联合有界整数模型，建立了一个 PK/PD 模型，将个体预测的尼古丁浓度与分类和视觉模拟 PD 量表联系起来。一个最大效应模型，考虑到急性耐受的发展，成功地将尼古丁浓度与即时渴望联系起来。结果表明，所有制剂在降低渴望方面同样有效，尽管贴片的效力低四倍。与男性相比，女性被发现有更高的降低渴望的尼古丁最大效应。
