Summary
Plasma samples from patients with prostatic cancer under oral treatment with estramustine phosphate (Estracyt®) were quantitatively analyzed for the presence of the parent drug and some of its possible metabolites. Specific methods based on radioimmunoassay and gas chromatography-mass fragmentography were used. Dephosphorylation and oxidation at the 17-position of estradiol were shown to be the major metabolic routes. The estrone analogue of estramustine was found to be the main metabolite in plasma. Elevated levels of estradiol and estrone showed that hydrolysis of the carbamic ester also occurred in these patients. Their estrogen levels were compared with those of another group of prostatic cancer patients receiving conventional hormonal therapy, polyestradiol phosphate (Estradurin ). Similar concentrations of estradiol were found in the two groups but the concentrations of estrone were higher in patients given estramustine phosphate.
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References
Jönsson G. and Högberg B. (1971): Treatment of advanced prostatic carcinoma with Estracyt. Scand. J. Urol. Nephrol.,5, 103–107.
Mittelman A., Shukla S.K. and Murphy G.P. (1976): Extended therapy of stage D carcinoma of the prostate with oral Estracyt. J. Urol.,115, 409–412.
Jönsson G., Högberg B. and Nilsson T. (1977): Treatment of advanced prostati~carcinoma with estramustine phosphate (Estracyt®). Scand. J. Urol. Nephrol.,11, 231–238.
Andersson L., Edsmyr F., Jönsson G. and Könyves T. (1977): Estramustine phosphate therapy in carcinoma of the prostate. Recent Results in Cancer Res.,60, 73–77.
Nagel R. and Kölin C.-P. (1977): Treatment of advanced carcinoma of the prostate with Estracyt. Br. J. Urol.,49, 73–79.
Von Hoff D.D., Rozencweig M., Slavik M. and Muggia F.M. (1977): Estramustine phosphate: A specific chemotherapeutic agent? J. Urol., 117. 464–466.
Kadohama N., Kirdani R.Y., Murphy G.P. and Sandberg A.A. (1978): Estramustine phosphate: Metabolic aspects related to its action in prostatic cancer. J. Urol.,119, 235–239.
Forsgren B., Gustafsson J.-A., Pousette A. and Högberg B.: Binding characteristics of a major protein in rat ventral prostate cytosol that interacts with estramustine, a nitrogen mustard derivative of estradiol-17β. Cancer Res., in press.
Högberg B., Björk P., Carlström R., Forsgren B., Gustafsson J.-A., Hökfelt T. and Pousette A. The interaction of steroidal alkylating agents with binding components in the soluble fraction of the prostate. In: Prostate Cancer and Hormone Receptors. Edited by Alan Liss Inc., New York, in press.
Kirdani R.Y., Mittelman A., Murphy C.P. and Sandberg A.A. (1975): Studies on phenolic steroids in human subjects. XIV. Fate of a nitrogen mustard of Estradiol-17β. J. Clin. Endocrinol. Metab.,41, 305–318.
Plym Forshell G., Müntzing J., Ek A., Lindstedt E. and Dencker H. (1976): The absorption, metabolism and excretion of Estracyt in patients with prostatic cancer. Invest. Urol.,14, 128–131.
Kirdani R.Y., Murphy G.P. and Sandberg A.A. (1977): Studies on a nitrogen mustard of estradiol in dogs and rats. Proc. Soc. Exp. Biol. Med.,155, 94–98.
Forsgren B., Gunnarsson P.O., Johansson S.-A. and Kant R. (1978): Radioimmunoassay of estramustine phosphate in plasma. Acta Pharm. Suec.,15, 200–210.
Andersson S.B., Lundgren R. and Svensson L. Gas chromatographic determination of the metabolites of estramustine phosphate in plasma. To be published.
Jönsson G. (1971): Treatment of prostatic carcinoma with polyestradiol phosphate combined with ethinylestradiol. Scand. J. Urol. Nephrol.,5, 97–102.
Brenner P.F., Guerrero R., Cekan Z. and Diczfalusy E. (1973): Radioimmunoassay method for six steroids in human plasma. Steroids,22, 775–794.
Loriaux D.L., Ruder H.J. and Lipsett M.B. (1971): The measurement of estrone sulphate in plasma. Steroids,18, 463–472.
Wu C.-H. and Lundy L.E. (1971): Radioimmunoassay of plasma estrogen. Steroids,18, 91–111.
Hawkins R.A. and Oakey R.E. (1974): Estimation of estrone sulphate, estradiol-17β and estrone in peripheral plasma: Concentrations during the menstrual cycle and in men. J. Endocrinol.,60, 3–17.
Jönsson G., Olsson A.M., Luttrop W., Cekan Z., Purvis K. and Diczfalusy E. (1975): Treatment of prostatic carcinoma with various types of estrogen derivatives. In: Vitamins and Hormones, vol. 33. International symposium on Endocrine control of the prostate. Munson P.L., Diczfalusy E., Glover J. and Olsson R.E. (eds), pp 351–376. Academic Press, New York, San Fransisco and London.
Fossa S.D., Fossa J. and Aakvaag A. (1977): Hormone changes in patients with prostatic carcinoma during treatment with estramustine phosphate. J. Urol.,118, 1013–1018.
Plym Forshell G. and Nilsson H. (1974): The distribution of radioactivity after administration of labelled estramustine phosphate (EstracytR), estradiol-17β-phosphate and estradiol to rats. Acta Pharmacol. Toxicol.,35, suppl. 1, 28.
Hoisaeter P.A. (1976): Studies on the conversion of estradiol linked to a cytostatic agent (EstracytR) in various rat tissues. Acta Endocrinol.,82, 661–672.
Appelgren L.-E., Forsgren B., Gustafsson J.-A., Pousette A. and Högberg B. (1977): Autoradiography of tritiated estramustine in castrated rats. Acta Pharmacol. Toxicol,41, suppl. 1, 106–107.
Müntzing J., Kirdani R.Y., Saroff J., Murphy G.P. and Sandberg A.A. (1977): Inhibitory effects of Estracyt on R-3327 rat prostatic carcinoma. Urol.,10, 439–445.
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Andersson, S.B., Gunnarsson, P.O., Nilsson, T. et al. Metabolism of estramustine phosphate (Estracyt ®) in patients with prostatic carcinoma. European Journal of Drug Metabolism and Pharmacokinetics 6, 149–154 (1981). https://doi.org/10.1007/BF03189482
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DOI: https://doi.org/10.1007/BF03189482