{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:56:08Z","timestamp":1792691768657,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>A physiologically\u2010based pharmacokinetic (PBPK) model of niraparib and its primary metabolite using a relevant virtual cancer population is reported here. A series of in\u00a0vitro experiments using liver S9, microsomes, and hepatocytes with various inhibitors and recombinant supersomes demonstrated that niraparib is specifically metabolized by carboxylesterase 1 via amide hydrolysis to an acid metabolite (M1). Available virtual cancer populations, along with reference populations, were applied to modeling simulations using fixed trial designs with demographic and clinical chemistry parameters from patients receiving niraparib in clinical studies. Simulations of niraparib and its metabolite M1 were verified across numerous available clinical studies and repeat dose ranges in cancer patients within 2\u2010fold. The PBPK model was used to simulate exposures in moderately hepatic impaired, healthy Chinese and Japanese virtual populations as a surrogate of cancer comorbidity. The PBPK model confirmed minimal DDI liability with niraparib as a precipitant for most in\u00a0vitro tested drug metabolizing enzymes and transporters. In\u00a0vitro, niraparib lacks any CYP inhibition, induces CYP1A2 but not CYP3A4, and is not a CYP substrate, unlike some other PARPi's, which inhibit and induce numerous enzymes\/transporters and are objects of CYP metabolism. At clinically relevant doses of niraparib \u2265\u2009200\u2009mg, a weak induction risk is predicted with sensitive CYP1A2 substrates, such as caffeine, and both niraparib and olaparib clinically increase serum creatinine in cancer patients, with up to a moderate inhibition risk predicted with MATE\u20101\/\u20102K substrates, such as metformin, using a PBPK model of niraparib in the absence of a dedicated DDI study.<\/jats:p>","DOI":"10.1002\/psp4.70182","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T08:18:28Z","timestamp":1768378708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Physiologically\u2010Based Pharmacokinetic Modeling of the\n                    <scp>PARP<\/scp>\n                    Inhibitor Niraparib"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8758-7421","authenticated-orcid":false,"given":"Gareth 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