PIP: A researcher in Helsinki, Finland conducted laboratory research on the pharmacokinetics, tissue distribution, serum binding properties, and binding affinities of RU-486 and its major metabolites. After oral administration of different single doses, absorption was rapid. RU-486 levels packed around 1 hour. Serum levels plateaued at 2.5 umol/1 for 24-48 hours and could still be measured for 5-7 days. There existed highly significant correlations between alpha1-acid glycoprotein (AAG), the main serum transport protein for RU-486, and serum concentrations of RU-486. As concentrations of RU-486 climbed from 2.5 umol/1, the available RU-486 for excretion or tissue distribution increased rapidly. Hence, AAG saturation may account for the similar serum concentrations of RU-486 following various doses. This also occurred following multiple doses of 50 mg RU-486. This phenomenon may explain why no correlation exists between the administration of RU-486 and clinical outcome when it is used to induce an abortion. RU-486 was detected in the myometrium at levels about 1/3 of those in serum, in fat at levels similar to those in serum, and in the enterohepatic cycle. The major metabolites retained moderate affinities of 9.21% to the progesterone receptor when compared with RU-486 (=100%). The inability of various doses to affect the clinical performance of RU-486 and the actions of RU-486 and its metabolites after oral intake suggest that the metabolites insignificantly affect the antiprogesterone action of RU-486. The affinities of these metabolites for the glucocorticoid receptor were higher (45-61%), however, perhaps causing the antiglucocorticoid effects of RU-486 at high oral doses. Based on these results, low doses of RU-486 (20-50 mg) could effectively terminate an early pregnancy.