title: [Drug therapy of metastasizing prostate carcinoma with special reference to the bioavailability of fosfestrol after oral administration].
abstract: 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.
authors.affiliation: Institut für Pharmazeutische Chemie, Johann Wolfgang Goethe-Universität, Frankfurt/Main.
authors.forename: H
authors.initials: H
authors.lastname: Oelschläger
authors.forename: D
authors.initials: D
authors.lastname: Rothley
authors.forename: U
authors.initials: U
authors.lastname: Dunzendorfer
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D001711:Biotransformation; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D055598:Chemical Phenomena; D002621:Chemistry; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004961:Estramustine / Q000627:therapeutic use; D004967:Estrogens / Q000627:therapeutic use; D006801:Humans; D007654:Ketoconazole / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010906:Pituitary Hormone-Releasing Hormones / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011485:Protein Binding
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D004967:Estrogens; D010906:Pituitary Hormone-Releasing Hormones; D004961:Estramustine; D004054:Diethylstilbestrol; C004955:fosfestrol; D007654:Ketoconazole
vernacular_title: Medikamentöse Therapie des metastasierenden Prostatakarzinoms unter besonderer Berücksichtigung der Bioverfügbarkeit von Fosfestrol nach oraler Gabe.