Plasma concentrations of estradiol and testosterone in single-drug polyestradiol phosphate therapy for prostatic cancer.

To evaluate the appropriate dosage of polyestradiol phosphate (PEP, Estradurin) as single-drug therapy, patients with metastatic prostatic carcinoma were given 80, 160 or 240 mg PEP every 4 weeks for at least 6 months. Injection of PEP was followed by rising plasma concentrations of estradiol in the first 2 weeks and slight fall in the next 2 weeks. Testosterone levels fell rapidly in the first 7 days and rose slightly in the following 3 weeks. Steady-state levels were reached after 2 months at the two lowest doses and after 4 months at the highest dose. Steady-state estradiol values increased in linear proportion to the dose. The steady-state concentrations of testosterone were about 45, 25 and 15% of the pretreatment values in the respective groups. At least 160 mg PEP at 4-week intervals is appropriate when the drug is used alone.

Pharmacokinetics of estramustine phosphate (Estracyt) in prostatic cancer patients.

The pharmacokinetics of estramustine phosphate (EMP) was studied in five prostatic cancer patients given single i.v. and oral doses of EMP in a cross-over study. Plasma and urinary concentrations of parent drug, estramustine, estromustine (the estrone analogue), estradiol and estrone were followed by 32 h. The elimination of intravenous EMP from plasma was biphasic. The mean volumes of distribution were small, being 43 and 108 ml/kg for the central and peripheral compartments, respectively. The plasma clearance was 64 ml/kg/h, and the half-lives of the two phases were 0.16 and 1.27 h. Metabolism was the major route of elimination of EMP. It was readily dephosphorylated and oxidized to yield the cytotoxic metabolites estramustine and estromustine. Estromustine was the main metabolite in plasma. When given orally EMP underwent extensive presystemic dephosphorylation, which started in the gastrointestinal tract. The relative bioavailability of estromustine after administration of EMP-capsules was 44%, which reflects incomplete absorption of EMP rather than first-pass metabolism of estromustine. The terminal half-life of estromustine was 10-20 h, which suggests that EMP might be given once or twice a day.