Pharmacodynamic model of testosterone suppression after intramuscular depot estrogen therapy in prostate cancer

BACKGROUND. A long-acting parenteral depot estrogen, polyestradiol phosphat e (PEP), which has been in clinical use for several years in combination th erapy, has been reevaluated pharmacokinetically and clinically as a single treatment. The present report describes a model predicting the effect on te stosterone flux achieved with this estrogen drug. METHODS. Data on serum levels of estradiol and testosterone from a single-d ose study, in prostate cancer patients as well as data from injections of 2 40 or 320 mg PEP each fourth week, were used for pharmacokinetic/dynamic mo deling. RESULTS. Serum concentrations of estradiol were governed by a flip-flop mec hanism when administered as PEP. An indirect-response model fitted to indiv idual data showed a value of about 500 pmol estradiol/l serum to get a 50% suppression of serum testosterone concentrations. CONCLUSIONS. This model could successfully predict the serum levels of estr adiol and testosterone after repeated injections at different doses and was also used to simulate the testosterone suppressing effect of a new dose re gimen. (C) 2000 Wiley-Liss.