Approaches to pharmacokinetic/ pharmacodynamic modeling during pregnancy.

The modern approach in the field of pharmacokinetics/pharmacodynamics is the development of models based on the mechanisms of drug action and their alteration of physiologic processes. Such models often require consideration of the input and disposition kinetics of the drug, distribution to sites of action (biophase), processes controlling receptor binding or mediator turnover, mechanisms of drug activity, and signal transduction steps. Responses can often be categorized as: Direct (rapidly or slowly reversible), Indirect (inhibitory or stimulatory), or Irreversible. Further, there may be alterations in the system owing to tolerance, counter-regulation, pathophysiology, or physiological changes such as gender or pregnancy. Mathematical and computational tools are necessary for processing data. This article overviews many available pharmacodynamic models with an indication of the diverse approaches for quantitation of pharmacologic responses. Examples from the literature are illustrated with emphasis on changes occurring in kinetics and dynamics during pregnancy.