The Pharmacokinetics/Pharmacodynamics (PK/PD) Core (Core B) provides mathematical modeling of datacollected in the three major projects. Core A contributes to the objectives of the SCOR by providing both data analysis and patient specific pharmacogenetic data to develop and test models describing the dose/ concentration-effect relationships of antidepressants (AD) and antiepileptic drugs (AED) used during pregnancy. For most drugs, pharmacokinetic and pharmacodynamic information is or at least should be the scientific basis for their clinical use. In pregnancy, the dynamic physiological changes that occur in the maternal/placental/fetal unit influence the processes of drug absorption, distribution and elimination leading to varying drug dosage requirements and uncertainty about the extent and consequences of fetal drug exposure. Through population pharmacokinetic modeling, we will identify sources of inter? and intraindividual variability in the concentration/time course of AD and AED from the administration of a certain dose. Fetal drug exposure will be predicted using maternal/umbilical cord concentrations obtained at birth. Covariables will be identified and rank ordered for importance that influence this exposure. A variety of effect measures corresponding to the primary disorder for which the AD and AED are being administered will be incorporated into the modeling process. These data analyses in Projects 1 & 2 will be complemented by animal experiments in Project 3 in which access to tissue drug concentrations unavailable in humans should allow further insight into factors influencing fetal drug exposure. Core A will apply the three major categories of pharmacokinetic models, compartmental, physiological and statistical, along with direct and indirect pharmacodynamic models, to explain and predict the role of maternal drug exposure to health and pregnancy outcomes.
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