{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:35:04Z","timestamp":1780479304488,"version":"3.54.1"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T00:00:00Z","timestamp":1489622400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T00:00:00Z","timestamp":1489622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001829","name":"Utrecht University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001829","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":[[2017,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Niraparib is an investigational oral, once daily, selective poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor. In the pivotal Phase 3 NOVA\/ENGOT\/OV16 study, niraparib met its primary endpoint of improving progression-free survival (PFS) for adult patients with recurrent, platinum sensitive, ovarian, fallopian tube, or primary peritoneal cancer in complete or partial response to platinum-based chemotherapy. Significant improvements in PFS were seen in all patient cohorts regardless of biomarker status. This study evaluates the absorption, metabolism and excretion (AME) of <jats:sup>14<\/jats:sup>C\u2013niraparib, administered to six patients as a single oral dose of 300\u00a0mg with a radioactivity of 100\u00a0\u03bcCi. Total radioactivity (TRA) in whole blood, plasma, urine and faeces was measured using liquid scintillation counting (LSC) to obtain the mass balance of niraparib. Moreover, metabolite profiling was performed on selected plasma, urine and faeces samples using liquid chromatography \u2013 tandem mass spectrometry (LC-MS\/MS) coupled to off-line LSC. Mean TRA recovered over 504\u00a0h was 47.5% in urine and 38.8% in faeces, indicating that both renal and hepatic pathways are comparably involved in excretion of niraparib and its metabolites. The elimination of <jats:sup>14<\/jats:sup>C\u2013radioactivity was slow, with t<jats:sub>1\/2<\/jats:sub> in plasma on average 92.5\u00a0h. Oral absorption of <jats:sup>14<\/jats:sup>C\u2013niraparib was rapid, with niraparib concentrations peaking at 2.49\u00a0h, and reaching a mean maximum concentration of 540\u00a0ng\/mL. Two major metabolites were found: the known metabolite M1 (amide hydrolysed niraparib) and the glucuronide of M1. Based on this study it was shown that niraparib undergoes hydrolytic, and conjugative metabolic conversions, with the oxidative pathway being minimal.<\/jats:p>","DOI":"10.1007\/s10637-017-0451-2","type":"journal-article","created":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T06:52:20Z","timestamp":1489647140000},"page":"751-765","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Human mass balance study and metabolite profiling of 14C-niraparib, a novel poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor, in patients with advanced cancer"],"prefix":"10.1007","volume":"35","author":[{"given":"Lotte","family":"van Andel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Kansra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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H.","family":"Beijnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,16]]},"reference":[{"key":"451_CR1","doi-asserted-by":"publisher","first-page":"7170","DOI":"10.1021\/jm901188v","volume":"52","author":"P Jones","year":"2009","unstructured":"Jones P, Altamura S, Boueres J et al (2009) Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. 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LA, MMT, AG, LL, MJXH, HR, JHMS and JHB are employed at the Netherlands Cancer Institute.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was funded by Tesaro, Inc.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the participating institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}