Relating nicotine plasma concentration to momentary craving across four nicotine replacement therapy formulations.

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 (PK) from NRTs and momentary craving, linking two different pharmacodynamic (PD) scales for measuring craving. The dataset comprised of 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 PKPD model was developed that linked individual predicted nicotine concentrations with the categorical and visual analogue PD scales through a joint bounded integer model. An Emax 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 a 4-fold lower potency for the patch. Females were found to have a higher maximal effect of nicotine to reduce craving, compared to males. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.