Exploration of Perinatal Pharmacokinetic Issues

In the process of reviewing current Agency toxicology testing paradigms for hazard characterization, the Risk Assessment Forum's (Forum) Reference Dose (RfD) Technical Panel became interested in evaluating the current pharmacokinetic data in immature animals, at various stages of development. To provide for this information, the Forum commissioned Versar, Inc. to develop an issue paper on five areas important to our understanding of perinatal pharmacokinetics in the unborn, infant, and young child. These areas include biotransformation, tissue distribution and excretion, transplacental transfer, plasma to milk transfer, and issues concerning the blood-brain barrier.

This paper brings together a large amount of previously disparate information. The first two sections of the paper cover relative activities and maturation of many enzyme systems, and relative tissue distribution and excretion capacities. The final sections provide specific information on transplacental transfer, plasma to milk transfer, and consideration of the blood-brain barrier. An understanding of these components and their impact on childhood exposures will be important to future model development and considerations of appropriate risk assessment approaches.

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