{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:39:09Z","timestamp":1787683149184,"version":"build-2784847793"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The poly(ADP\u2010ribose) polymerase inhibitor talazoparib, combined with the androgen receptor inhibitor enzalutamide is approved for patients with homologous recombination repair (HRR) gene\u2010mutated metastatic castration\u2010resistant prostate cancer (mCRPC) in the US and with mCRPC in whom chemotherapy is not clinically indicated in Europe. We provide a population pharmacokinetic model for this combination in patients with mCRPC unselected for HRR deficiencies from TALAPRO\u20102 (NCT03395197). The pooled dataset included 811 patients treated with enzalutamide plus either talazoparib or placebo. The final enzalutamide model was a two\u2010compartment model with first\u2010order absorption and inter\u2010individual variability (IIV) on apparent clearance (CL\n                    <jats:sub>e<\/jats:sub>\n                    \/F\n                    <jats:sub>e<\/jats:sub>\n                    ) and apparent central volume of distribution (Vc\n                    <jats:sub>e<\/jats:sub>\n                    \/F\n                    <jats:sub>e<\/jats:sub>\n                    ) and included effects of baseline body weight and age on CL\n                    <jats:sub>e<\/jats:sub>\n                    \/F\n                    <jats:sub>e<\/jats:sub>\n                    and Vc\n                    <jats:sub>e<\/jats:sub>\n                    \/F\n                    <jats:sub>e<\/jats:sub>\n                    . For the active metabolite N\u2010desmethyl enzalutamide, a two\u2010compartment model with IIV on CL\n                    <jats:sub>n<\/jats:sub>\n                    and Vc\n                    <jats:sub>n<\/jats:sub>\n                    adequately described the observed data and included the effect of body weight on CL\n                    <jats:sub>n<\/jats:sub>\n                    and Vc\n                    <jats:sub>n<\/jats:sub>\n                    . The final talazoparib model was well characterized by a two\u2010compartment model with first\u2010order absorption and IIV on talazoparib apparent base clearance (CL\n                    <jats:sub>t0<\/jats:sub>\n                    \/F\n                    <jats:sub>t<\/jats:sub>\n                    ) and Vc\n                    <jats:sub>t<\/jats:sub>\n                    \/F\n                    <jats:sub>t<\/jats:sub>\n                    . The effect of enzalutamide and N\u2010desmethyl enzalutamide on CL\n                    <jats:sub>t<\/jats:sub>\n                    \/F\n                    <jats:sub>t<\/jats:sub>\n                    of talazoparib was modeled through a linear relationship. The single covariate effect of baseline creatinine clearance on CL\n                    <jats:sub>t0<\/jats:sub>\n                    \/F\n                    <jats:sub>t<\/jats:sub>\n                    showed that relative to the reference value for normal renal function, CL\n                    <jats:sub>t0<\/jats:sub>\n                    \/F\n                    <jats:sub>t<\/jats:sub>\n                    decreased by 8% for mild, 27% for moderate, and 46.7% for severe renal impairment. Simulations showed that a dose reduction of enzalutamide does not require talazoparib dose modification since the magnitude of exposure reduction for talazoparib was not considered clinically significant.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70125","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:39:51Z","timestamp":1764052791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Population Pharmacokinetics Analysis of Talazoparib and Enzalutamide Combination Therapy for Patients With Metastatic Castration\u2010Resistant Prostate Cancer"],"prefix":"10.1002","volume":"66","author":[{"given":"Mark","family":"Hadigol","sequence":"first","affiliation":[{"name":"Oncology Early Stage Development (OESD) \u2014 Clinical Pharmacology Pfizer Inc.  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason H.","family":"Williams","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Pharmacometrics Exelixis Inc.  King of Prussia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Shi","sequence":"additional","affiliation":[{"name":"Clinical Assay Group \u2013 Translational Clinical Sciences Pfizer Inc.  Groton CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek Z.","family":"Yang","sequence":"additional","affiliation":[{"name":"Oncology Early Stage Development (OESD) \u2014 Clinical Pharmacology Pfizer Inc.  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Oncology Early Stage Development (OESD) \u2014 Clinical Pharmacology Pfizer Inc.  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane D.","family":"Wang","sequence":"additional","affiliation":[{"name":"Oncology Early Stage Development (OESD) \u2014 Clinical Pharmacology Pfizer Inc.  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1391"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-13-0803"},{"key":"e_1_2_10_6_1","volume-title":"TALZENNA\u00ae (talazoparib capsule) prescribing information","author":"Pfizer Inc"},{"key":"e_1_2_10_7_1","volume-title":"XTANDI\u00ae (enzalutamide) prescribing information","author":"Pfizer Inc"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2021-0811"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01055-3"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02704-x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14178"},{"key":"e_1_2_10_12_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM).Guidance for Industry: Bioanalytical Method Validation. 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