DataSheet1_Physiologically Based Pharmacokinetic Modelling for Nicotine and Cotinine Clearance in Pregnant Women.PDF

Introduction: Physiologically based pharmacokinetic (PBPK) models for the absorption, disposition, metabolism and excretion (ADME) of nicotine and its major metabolite cotinine in pregnant women (p-PBPK) are rare. The aim of this short research report is to present a p-PBPK model and its simulations for nicotine and cotinine clearance.Methods: The maternal-placental-fetal compartments of the p-PBPK model contain a total of 16 compartments representing major maternal and fetal organs and tissue groups. Qualitative and quantitative data of nicotine and cotinine disposition and clearance have been incorporated into pharmacokinetic parameters.Results: The p-PBPK model reproduced the higher clearance rates of nicotine and cotinine in pregnant women than non-pregnant women. Temporal profiles for their disposition in organs such as the brain were also simulated. Nicotine concentration reaches its maximum value within 2 min after an intravenous injection.Conclusion: The proposed p-PBPK model produces results consistent with available data sources. Further pharmacokinetic experiments are required to calibrate clearance parameters for individual organs, and for the fetus.

引言：针对孕妇体内尼古丁及其主要代谢物可替宁的吸收、分布、代谢和排泄（ADME）的生理学基础药代动力学（PBPK）模型极为罕见。本短篇研究报告旨在介绍一个p-PBPK模型及其对尼古丁和可替宁清除率的模拟。方法：该p-PBPK模型包含母体-胎盘-胎儿三个部分，共计16个部分，代表主要的母体和胎儿器官及组织群。尼古丁和可替宁的分布与清除的定性及定量数据已被整合入药代动力学参数中。结果：所提出的p-PBPK模型成功地再现了孕妇相较于非孕妇，尼古丁和可替宁清除率更高的现象。对器官如大脑中其分布的时间曲线也进行了模拟。静脉注射后2分钟内，尼古丁浓度达到峰值。结论：所提出的p-PBPK模型所产生的结果与现有数据来源一致。为进一步校准个体器官和胎儿清除率参数，需要进行进一步的药代动力学实验。