{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T06:25:16Z","timestamp":1778048716444,"version":"3.51.4"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T00:00:00Z","timestamp":1554249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Takeda Development Centre Europe Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This investigation aimed to quantitatively characterize the relationship between the gonadotropin\u2010releasing hormone agonist leuprorelin, testosterone (T) and prostate specific antigen (PSA) concentrations over time, to aid identification of a target T concentration that optimises the balance of the benefits of T suppression whilst reducing the risk of side effects related to futile over\u2010suppression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from a single dose study to investigate the effect of leuprorelin in a 6\u2010month depot formulation on T and PSA in prostate cancer patients were analysed using a population pharmacokinetic\u2013pharmacodynamic modelling approach. The developed model was qualified using external data from 3 studies, in which the effect of different formulations of leuprorelin on T and PSA was evaluated in prostate cancer patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The effect of leuprorelin on the relationship between T and PSA was adequately characterized by the Romero model with minor modifications, combined with a turnover model to describe the delay in response between T and PSA. The data were significantly better described when assuming a minimum PSA level that is independent on the treatment\u2010related reduction in T, as compared to a model with a proportional reduction in PSA and T.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The model\u2010based analysis suggests that on a population level, reducing T concentrations below 35\u00a0ng\/dL does not result in a further decrease in PSA levels (&gt;95% of the minimal PSA level is reached). More data are required to support this relationship in the lower T and PSA range.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13891","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T23:45:59Z","timestamp":1549583159000},"page":"1247-1259","source":"Crossref","is-referenced-by-count":7,"title":["Population pharmacokinetic\u2013pharmacodynamic modelling of the relationship between testosterone and prostate specific antigen in patients with prostate cancer during treatment with leuprorelin"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1302-678X","authenticated-orcid":false,"given":"Nelleke","family":"Snelder","sequence":"first","affiliation":[{"name":"LAP&amp;P Consultants BV  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henk\u2010Jan","family":"Drenth","sequence":"additional","affiliation":[{"name":"LAP&amp;P Consultants BV  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten","family":"Riber Bergmann","sequence":"additional","affiliation":[{"name":"LAP&amp;P Consultants BV  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nolan David","family":"Wood","sequence":"additional","affiliation":[{"name":"Takeda Development Centre Europe Ltd  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Hibberd","sequence":"additional","affiliation":[{"name":"Takeda Development Centre Europe Ltd  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham","family":"Scott","sequence":"additional","affiliation":[{"name":"Takeda Development Centre Europe Ltd  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/RRU.S111475"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(00)00793-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.05.129"},{"issue":"12","key":"e_1_2_9_5_1","first-page":"1168","article-title":"Efficacy and safety of leuprorelin acetate 6\u2010month depot in prostate cancer patients: a Phase III, randomized, open\u2010label, parallel\u2010group, comparative study in Japan","volume":"45","author":"Suzuki K","year":"2015","journal-title":"Jpn J Clin Oncol"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-12-0040"},{"issue":"19","key":"e_1_2_9_7_1","first-page":"1518","article-title":"Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer","volume":"104","author":"Keating NL","year":"2012","journal-title":"J Natl Cancer Inst"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/35094009"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21989"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22464"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/pcan.2008.52"},{"key":"e_1_2_9_12_1","unstructured":"Nicholasbruchovsky.com [homepage on the internet]. 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