[Pharmacokinetics of RU 486 and its active metabolites in humans]

The pharmacokinetics of RU 486 and its active metabolites were studied in 31 women who received a single oral dose of 200 mg (n = 9), 400 mg (n = 10) or 600 mg (n = 12) of RU 486 for termination of an early unwanted pregnancy. The serum levels were measured within 48 hours after the intake by radioligand binding assay using human myometrial cytosolic progesterone receptor as binding protein. The assay is based on the competitive replacement of 3H-ORG-2058 by the active molecular fraction of RU 486 present in the serum. The results were expressed as RU 486 equivalent. It was found that pharmacokinetics of the RU 486 equivalent followed two-compartment open model. The pharmacokinetic parameters were calculated by MEDUSA computer programme. Rapid absorption and distribution was followed by relatively slow elimination. The elimination half-life ranged between 80-90 hours. No significant difference was found between the parameters of the absorption distribution and elimination processes of three different doses. Thus, the RU 486 equivalent followed first-order kinetic. Peak serum concentrations were reached within 1-2 hours after the ingestion of the drug. Significant differences were found between 200 and 600 mg doses in the peak plasma values (p < 0.05) and in the areas under the curve (p < 0.01). However, these differences were not directly proportional to the increase of the dose.