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Pharmacodynamic model of testosterone suppression after intramuscular depot estrogen therapy in prostate cancer
Author(s) -
Johansson C.J.,
Gunnarsson P.O.
Publication year - 2000
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/1097-0045(20000615)44:1<26::aid-pros4>3.0.co;2-p
Subject(s) - testosterone (patch) , medicine , pharmacodynamics , prostate cancer , estrogen , endocrinology , prostate , pharmacokinetics , regimen , cancer
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. Prostate 44:26–30, 2000. © 2000 Wiley‐Liss, Inc.