{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T21:47:05Z","timestamp":1781819225274,"version":"3.54.5"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T00:00:00Z","timestamp":1561593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T00:00:00Z","timestamp":1561593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100014487","name":"Clovis Oncology","doi-asserted-by":"crossref","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100014487","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Rucaparib, a poly(ADP-ribose) polymerase inhibitor, is licensed for use in recurrent ovarian, fallopian tube, or primary peritoneal cancer. We characterized the absorption, distribution, metabolism, and elimination of rucaparib in 6 patients with advanced solid tumors following a single oral dose of [<jats:sup>14<\/jats:sup>C]-rucaparib 600\u00a0mg (\u2248140\u00a0\u03bcCi). Total radioactivity (TRA) in blood, plasma, urine, and feces was measured using liquid scintillation counting. Unchanged rucaparib concentrations in plasma were determined using validated liquid chromatography with tandem mass spectrometry. Maximum concentration (C<jats:sub>max<\/jats:sub>) of TRA and unchanged rucaparib in plasma was 880\u00a0ng\u00a0Eq\/mL and 428\u00a0ng\/mL, respectively, at approximately 4\u00a0h post dose; terminal half-life was &gt;25\u00a0h for both TRA and rucaparib. The plasma TRA-time profile was parallel to yet higher than that of rucaparib, suggesting the presence of metabolites in plasma. Mean blood:plasma ratio of radioactivity was 1.0 for C<jats:sub>max<\/jats:sub> and 0.8 for area under the concentration-time curve from time zero to infinity. Mean postdose recovery of TRA was 89.3% over 12\u00a0days (71.9% in feces; 17.4% in urine). Unchanged rucaparib and M324 (oxidative metabolite) were the major components in plasma, contributing to 64.0% and 18.6% of plasma radioactivity, respectively. Rucaparib and M324 were the major rucaparib-related components (each \u22487.6% of dose) in urine, whereas rucaparib was the predominant component (63.9% of dose) in feces. The high fecal recovery of unchanged rucaparib could be attributed to hepatic excretion and\/or incomplete oral absorption. Overall, these data suggest that rucaparib is eliminated through multiple pathways, including metabolism and renal and biliary excretion.<\/jats:p>","DOI":"10.1007\/s10637-019-00815-2","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T07:45:48Z","timestamp":1561621548000},"page":"765-775","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Evaluation of absorption, distribution, metabolism, and excretion of [14C]-rucaparib, a poly(ADP-ribose) polymerase inhibitor, in patients with advanced solid tumors"],"prefix":"10.1007","volume":"38","author":[{"given":"Mingxiang","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Nash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Isaacson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Etter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeri","family":"Beltman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Mutlib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vendel","family":"Kemeny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"P\u00e1pai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"van Tilburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3632-2012","authenticated-orcid":false,"given":"Jim J.","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,27]]},"reference":[{"key":"815_CR1","unstructured":"Rubraca (rucaparib) tablets [prescribing information] (2018). Clovis Oncology, Inc., Boulder, CO, USA"},{"key":"815_CR2","doi-asserted-by":"crossref","unstructured":"Farmer H, McCabe N, Lord CJ, Tutt ANJ, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NMB, Jackson SP, Smith GCM, Ashworth A (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434(7035):917\u2013921.\u00a0https:\/\/doi.org\/10.1038\/nature03445","DOI":"10.1038\/nature03445"},{"key":"815_CR3","doi-asserted-by":"crossref","unstructured":"Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434(7035):913\u2013917. https:\/\/doi.org\/10.1038\/nature03443","DOI":"10.1038\/nature03443"},{"key":"815_CR4","unstructured":"Rubraca (rucaparib) tablets [summary of product characteristics] (2019). Clovis Oncology Ireland Ltd., Swords, Ireland"},{"issue":"15","key":"815_CR5","doi-asserted-by":"publisher","first-page":"4095","DOI":"10.1158\/1078-0432.CCR-16-2796","volume":"23","author":"R Kristeleit","year":"2017","unstructured":"Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmana J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R (2017) A phase I-II study of the oral PARP inhibitor rucaparib in patients with germline BRCA1\/2-mutated ovarian carcinoma or other solid tumors. Clin Cancer Res 23(15):4095\u20134106. https:\/\/doi.org\/10.1158\/1078-0432.CCR-16-2796","journal-title":"Clin Cancer Res"},{"issue":"1","key":"815_CR6","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1002\/cpdd.575","volume":"8","author":"GI Shapiro","year":"2018","unstructured":"Shapiro GI, Kristeleit R, Burris HA, LoRusso P, Patel MR, Drew Y, Giordano H, Maloney L, Watkins S, Goble S, Jaw-Tsai S, Xiao J (2018) Pharmacokinetic study of rucaparib in patients with advanced solid tumors. Clin Pharmacol Drug Dev 8(1):107\u2013118. https:\/\/doi.org\/10.1002\/cpdd.575","journal-title":"Clin Pharmacol Drug Dev"},{"key":"815_CR7","unstructured":"Center for Drug Evaluation and Research (2017) Multi-discipline review\/summary, clinical, non-clinical for NDA 209115. U.S. Department of Health and Human Services; Food and Drug Administration; Center for Drug Evaluation and Research. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2016\/209115Orig1s000MultiDisciplineR.pdf. 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Drug Metab Dispos 42(12):2023\u20132032. https:\/\/doi.org\/10.1124\/dmd.114.059675","journal-title":"Drug Metab Dispos"}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-019-00815-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-019-00815-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-019-00815-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T04:35:58Z","timestamp":1678509358000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-019-00815-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,27]]},"references-count":11,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["815"],"URL":"https:\/\/doi.org\/10.1007\/s10637-019-00815-2","relation":{},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,27]]},"assertion":[{"value":"6 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 June 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"<b>ML, SW, JI, JE, JB,<\/b> and <b>JJX<\/b> are employees of Clovis Oncology and may own stock or have stock options in that company. <b>EN<\/b> is a paid consultant for Clovis Oncology. <b>RF, LS,<\/b> and <b>AM<\/b> are employees of Frontage Laboratories and may own stock or have stock options in that company. <b>VK<\/b> and <b>PVT<\/b> are employees of PRA Health Sciences and may own stock or have stock options in that company. <b>ZP<\/b> has nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}