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Pharmacodynamic model of testosterone suppression after intramuscular depot estrogen therapy in prostate cancer
C J Johansson1, P O Gunnarsson
1AstraDraco R&D, Lund, Sweden.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
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