Bioavailability, Distribution and Pharmacokinetics of Diethylstilbestrol Produced from Stilphostrol

Abstract

The kinetic behavior of diethylstilbestrol (DES) produced from stilphostrol was studied in man, dog and rat. A sensitive and selective assay for DES in plasma and tissues was developed with the use of gas chromatographic separation and mass spectrometric detection. In patients with prostate cancer, the plasma concentrations of DES produced by 1000-mg infusions of stilphostrol are 1500 times the DES concentrations produced by conventional oral DES doses. The pharmacokinetics of DES show 2 separate phases, one with a t1/2 [half-life] of .apprx. 1 h and another with a t1/2 of .apprx. 1 day. In rats, stilphostrol does not selectively liberate DES in the prostate compared to dosing with DES itself. In dogs, a 50-mg tablet of stilphostrol was bioequivalent to 40 mg of DES taken orally. Evidently, the high DES concentrations produced by stilphostrol infusions result in its ability to produce objective responses in patients refractory to conventional oral DES therapy.