The contribution of transplacental clearances and fetal clearance to drug disposition in the ovine maternal-fetal unit.

The total clearance of drugs from the fetus is the sum of clearance by the placenta from fetus to mother and clearance by nonplacental mechanisms such as renal excretion and biotransformation. Representing the maternal-fetal unit by a general two-compartment open model, we have derived equations for the calculation of placental and nonplacental drug clearances from the maternal compartment and fetal compartment under steady-state conditions. The equations suggest that fetal drug elimination to the exterior would result in a maternal-fetal concentration gradient at steady state after maternal drug administration. These equations have been applied to the study of methadone disposition in the ovine maternal-fetal unit.