Physiologically-based pharmacokinetic model for pregnancy as a tool for investigation of developmental mechanisms.
There is no known mechanism of teratogenesis! Although receptor occupancy has been implicated, associated and/or deemed necessary for some malformations in newborns (e.g. estrogen receptors, retinoic acid receptors), the upstream and downstream events from receptor occupancy that definitively tie a xenobiotic exposure with a resultant malformation are essentially unknown. One part of the puzzle that can be delineated is the xenobiotic target-tissue exposure curve. Physiologically-based pharmacokinetic (PBPK) models are designed to provide time-course exposure curves for organs, tissues and fluids of human or animal systems. In this context pregnancy requires special considerations in that the PBPK model must represent the dynamic growth of both the maternal and embryo/fetal systems.
Young
J F
JF
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA. jyoung@nctr.fda.gov
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D003198:Computer Simulation; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D006801:Humans; D018811:Maternal Exposure / Q000009:adverse effects*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D008954:Models, Biological; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011955:Receptors, Drug / Q000502:physiology; D015203:Reproducibility of Results; D012377:Rodentia; D013723:Teratogens / Q000493:pharmacokinetics*; D013997:Time Factors; D015262:Xenobiotics / Q000009:adverse effects* / Q000493:pharmacokinetics*
D011955:Receptors, Drug; D013723:Teratogens; D015262:Xenobiotics