AUTHOR=Amice Basile , Ho Harvey , Zhang En , Bullen Chris 

TITLE=Physiologically Based Pharmacokinetic Modelling for Nicotine and Cotinine Clearance in Pregnant Women

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.688597

DOI=10.3389/fphar.2021.688597

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> 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.</p>