| Apparent initial volume
of distribution after intravenous administration of mifepristone 280mg was low at 8L but
at a steady state was 25.7L¹. The volume of distribution and clearance of mifepristone
were inversely proportional to the plasma concentrations of AAG, being greater in subjects
with low AAG levels, and are dose - and time dependent. At plasma concentrations of up to 0.8mg/L mifepristone is about 98% bound to plasma proteins in the blood. Its binding to erythrocytes is negligible². A value of 94% was reported at a plasma mifepristone concentration of 5mg/L (Kawai et al. 1987). It is considered that AAG is the principal binding protein for mifepristone ³. When binding to AAG is saturated, mifepristone and its metabolites bind to albumin (Grimaldi et al. 1989). The concentration of mifepristone in the cerebral spinal fluid of proteins with Cushings syndrome receiving high dosages of the drug was 4% the concurrent concentration (Kawai et al.1987). Mifepristone crosses the placenta. Cord blood concentrations were about one-third of maternal blood concentrations 4 while the maternal: fetal ratios in plasma for mifepristone and its monodemethylated metabolite were 9:1 and 17:1, respectively (Hill et al. 1990). Fetal aldosterone levels were elevated 4 and 24 hours after maternal ingestion's of mifepristone 600mg but the drug did not affect progesterone, stradiol or cortisol levels (5). |
