Determination of RU486 (mifepristone) in blood by radioreceptorassay; a pharmacokinetic study

A human progesterone receptor assay has been developed for the measurement of the biologically active molecular fraction of RU486 (RU486 binding equivalent) for studying its pharmacokinetic properties. Thirty-nine healthy pregnant volunteers with amenorrhoea of 49 days or less receiving a single oral dose of 200 mg, 400 mg or 600 mg RU486 orally in a single dose were involved in this study. Blood samples were collected within 48 hours for the analysis. It was found that the pharmacokinetics of the RU486 binding equivalent followed an open two-compartment model. The dose was rapidly absorbed and peak serum concentrations were measured within 1-2 hours after ingestion of the drug. The distribution was also rapid, but the elimination was slow, the elimination half-life ranging between 83 and 90 hours. Significant differences were found between the peak plasma values for the 200 mg and 600 mg doses (p < 0.05) and between the AUCs for the 200 mg and 600 mg doses (p < 0.01) and the 400 mg and 600 mg doses (p < 0.05). It can be concluded that this newly developed radioreceptor assay satisfies the requirements of radioligand binding techniques and can be used to determine the serum levels of RU486 and its metabolites, which are able to bind to human myometrial progesterone receptors. The pharmacokinetics for the RU486 binding equivalent is similar to that for RU486, with the exception of very slow elimination, which may originate from the measurement of the biologically active metabolites together with the parent compound.