A PBPK model for the clearance of nicotine and cotinine in pregnant women

Active or passive maternal smoking causes many adverse effects on fetuses. Pregnancy-related physiologically based pharmacokinetic (p-PBPK) models could help interpret nicotine and its major metabolite cotinine‘s absorption, disposition, metabolism, and excretion (ADME) in pregnant women. This talk presents a p-PBPK model and its simulations for nicotine and cotinine. The maternal-placental-fetal compartments of the p-PBPK model contain 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. The p-PBPK model reproduced the higher clearance rates of nicotine and cotinine in pregnant women than non-pregnant women. Nicotine concentration reaches its maximum value within 2 min after intravenous injection in organs such as the brain. In conclusion, the proposed p-PBPK model is the first of its kind, and simulation results are consistent with available data. Further pharmacokinetic experiments are required to calibrate clearance parameters for individual organs and the fetus.