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

Abstract

A long-acting parenteral depot estrogen, polyestradiol phosphate (PEP), which has been in clinical use for several years in combination therapy, has been reevaluated pharmacokinetically and clinically as a single treatment. The present report describes a model predicting the effect on testosterone flux achieved with this estrogen drug. Data on serum levels of estradiol and testosterone from a single-dose study, in prostate cancer patients as well as data from injections of 240 or 320 mg PEP each fourth week, were used for pharmacokinetic/dynamic modeling. Serum concentrations of estradiol were governed by a flip-flop mechanism when administered as PEP. An indirect-response model fitted to individual data showed a value of about 500 pmol estradiol/l serum to get a 50% suppression of serum testosterone concentrations. This model could successfully predict the serum levels of estradiol and testosterone after repeated injections at different doses and was also used to simulate the testosterone suppressing effect of a new dose regimen.