Prostata
cancer is one of the most dangerous tumours occurring in the older man. No general accepted
therapy has existed up to now. In this study we were engaged on the pharmacokinetics of
fosfestrol (
Honvan) after
oral administration. Its active principle is E-
diethylstilbestrol (E-DES), the main metabolite. 250-1600 ng/ml E-DES are measurable after 60-110 min in the plasma of 11 patients suffering from metastatic prostata
cancer who have been administered 360 mg
fosfestrol orally. This range is equivalent to E-DES concentrations in plasma of 1-4 x 10(-6) mol/l. Thus that E-DES concentration range (5 x 10(-6) mol/l) is nearly attained for a short time to the concentration which hinders the mitosis of human
breast cancer cells. Surprisingly similar but not higher concentration - time courses may be measured after a bolus infusion of 360 mg
fosfestrol (lasting 45 min). Furthermore, E-DES-
glucuronide, E-DES-sulphate and the mixed E-DES-
glucuronide-sulphate could be observed in plasma after
oral administration. In spite of the high sensitivity of the analytical method (limit of detection for
fosfestrol 0.1 micrograms/ml and for E-DES and its mono-conjugates 2-5 ng/ml) neither
fosfestrol nor E-DES-monophosphate are detectable in plasma due to the biotransformation of
fosfestrol, which is already metabolized by the
enzymes of the gut wall. Both
phosphates only exist in plasma after
intravenous infusion. Further investigations are linked with the question if phase II-conjugates of E-DES can eventually be
prodrugs delivering E-DES by cleavage of the
ester bonds.