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

Abstract

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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.

Keywords

• nicotine
• cotinine
• pregnant women
• fetus
• PBPK