New Results on the Pharmacokinetics of Fosfestrol

Abstract

For more than 30 years Fosfestrol (Honvan®) has been used as an estrogen for successful palliative therapy of prostatic carcinoma, but the pharmacokinetics of this compound were unknown due to the lack of analytical methods. Over the last few years we have developed a special extraction process for Fosfestrol and its metabolites from plasma with recovery yields > 90%. The simultaneous measurement of the most important compounds after intravenous and oral administration was achieved by high-performance liquid chromatography, either with the UV detector (236 nm) or with an electrochemical detector (+ 1 V). The working electrode is a carbon paste electrode constructed in this laboratory; the counter electrode is an Au and the reference electrode an Ag/AgCl electrode. The electrode processes have been clarified. Fosfestrol and its monophosphate exist only for a short time in small amounts in the circulating blood after intravenous administration, whilst after oral administration, not even traces of the phosphates could be detected in the plasma. The most important influence on plasma levels of Fosfestrol and its metabolites is due to the extraction function of the liver. Diethylstilbestrol conjugates enter into the enterohepatic circle, thus forming a possible source of DES available over more than 24 h. Only DES glucuronide and DES glucuronide-sulphate are renally eliminated and could be detected after administration over 3 days.

Investigations of Interactions of Chlormezanone Racemate and Its Enantiomers on Human Keratinocytes and Human Leucoytes in vitro

“…Previous studies showed that the enantiomers differ in their t 1/2 value considerably [12]. The present investigation analyzed cell biologic effects of chlormezanone racemate and (+)-and (-)-enantiomers in vitro.…”

“…1). Other pharmacological and pharmacokinetic qualities are not specific for any of the enantiomers [11][12][13][14][15][16][17].…”

Use of intravenous fosfestrol tetrasodium (Honvan) infusion in treatment of symptomatic advanced prostate cancer

“…4 From the point of view of thrombotic events, our series reiterates the experience of a number of studies, 5 and there is evidence that the intravenous route may even be safer than the oral route. 6 Pharmacokinetic studies 7 have demonstrated that peak plasma levels of fosfestrol are achieved very quickly, with rapid clearance of the principal metabolites. Pharmacokinetic pro®les seem not to be affected by daily repeated administration, nor by renal impairment, an important determinant given the ages of our patients and obvious tendencies towards renal impairment.…”

Assay of the synthetic estrogen fosfestrol in pharmaceutical formulations using capillary electrophoresis

“…So far, the reported fosfestrol assays are based on high performance liquid chromatography (HPLC) [4][5][6][7][8][9], batch [10,11] and automated spectrophotometry using flow injection analysis [12][13][14]. Capillary electrophoresis (CE) is a relatively "young" technique [15,16] gaining continuously growing attention and acceptance among scientists due to its unique features and advantages over traditional liquid chromatographic separation techniques.…”