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

Abstract

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.

Environmental tobacco smoke at home and in public places prior to smoking ban enforcement: Assessment by hair analysis in a population of young adult students

“…According to the regression line, cotinine concentration was equal to “0.031 × nicotine + 0.09.” This observation is in agreement with previous studies analyzing these two compounds in hair and also reporting higher concentration of nicotine 12,29,30 . This difference is surprising because cotinine is the major metabolite of nicotine and usually presents comparable or higher concentration in plasma 8,31,32 . Nevertheless, the higher concentration of nicotine might not be due to deposition on hair surface from air because hair samples were washed before analysis in order to remove chemicals possibly deposited on hair.…”

“…12,29,30 This difference is surprising because cotinine is the major metabolite of nicotine and usually presents comparable or higher concentration in plasma. 8,31,32 Nevertheless, the higher concentration of nicotine might not be due to deposition on hair surface from air because hair samples were washed before analysis in order to remove chemicals possibly deposited on hair. The higher concentration of nicotine compared to cotinine could therefore be attributed to differences in incoportation rate or mechanism, as already observed for compounds with different physicochemical porperties.…”

In silico modeling for the hepatic circulation and transport: From the liver organ to lobules

“…Pharmacokinetics (PK) studies the absorption, distribution, metabolism, and excretion (ADME) of a drug in an organism (Barrett et al, 2012; Jones & Rowland‐Yeo, 2013; Köller et al, 2021), and the liver's central role in drug metabolism and excretion gives it particular prominence. In a typical physiologically based pharmacokinetic (PBPK) model, the concentration of a drug in the liver is represented in a single compartment (Amice et al, 2021). However, the liver tissue, sinusoidal volume, and biliary tracts are also modeled as separate PBPK models on their own (Audebert & Vignon‐Clementel, 2018; Liu & Pang, 2006).…”

Secondhand Smoking and Sudden Infant Death Syndrome: How can in Silico Pharmacokinetics and Circulation Models Contribute?

“…Differential equations are formulated to model the changes in the amount or concentration of a compound in that compartment ( Jones and Rowland-Yeo, 2013 ). Paediatric PBPK ( p -PBPK) models incorporate the physiological and metabolic differences between adults and children, such as the blood flow distribution in individual organs, age-dependent enzyme activities and renal clearance ( Amice et al, 2021 ) ( Zhang et al, 2020 ).…”

“…PBPK models of nicotine and cotinine have been recently reported for pregnant women ( Amice et al, 2021 ). However, few in silico studies report the clearance of nicotine and cotinine, the major metabolite of nicotine, in neonates and infants ( Gentry et al, 2003 ).…”