{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:08:37Z","timestamp":1784099317751,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011851","name":"Kom op tegen Kanker","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011851","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003441","name":"Universitair Ziekenhuis Gent","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003441","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To characterize the pharmacokinetics (PK), metabolite kinetics and toxicity risk of nanoparticle albumin\u2010bound paclitaxel (Nab\u2010PTX) administered via pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal metastasis, using data from a Phase 1 trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Twenty patients received two to three Nab\u2010PTX PIPACs at doses ranging from 35 to 140\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      with a four\u2010week dosing interval. A population pharmacokinetic\u2010pharmacodynamic model was developed describing plasma concentrations of paclitaxel and metabolites (6\u2010hydroxy and 3\u2010hydroxy paclitaxel) and neutrophil dynamics. Bioavailability was estimated based on published intravenous data. Logistic regression was used to relate paclitaxel exposure to hepatotoxicity events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A two\u2010compartment model with zero\u2010order input best describes paclitaxel PK, with an estimated absorption duration of 3.49\u2009h. Bioavailability was estimated at 37.0%. The total apparent volume of distribution of the two\u2010compartment system was 2299\u2009L. The population apparent clearance was 87.3\u00a0L\/h and was accompanied by moderate variability between subjects and occasions (23.9 and 29.5% CV, respectively). Rate constants of metabolite formation and elimination displayed more extensive variability (52.6%\u201395.1% CV). Body surface area was incorporated as a covariate on apparent clearance.. Paclitaxel maximum concentrations and total exposure were associated with bilirubin and ALT adverse events, respectively, but not with other hepatotoxicity events. Dosing simulations predicted a low risk (0.8%) of grade 4 neutropenia at the highest investigated dose, with neutrophil nadirs at day 10 and recovery within 3\u20134\u00a0weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The developed model justifies a 140\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      Phase 2 dose characterized by slow absorption and tolerable dose\u2010related haematological and hepatic toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70529","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:51:54Z","timestamp":1773766314000},"page":"2336-2348","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics and pharmacodynamics of intraperitoneal aerosolized nanoparticle albumin\u2010bound paclitaxel (nab\u2010PTX) and metabolites"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-8017","authenticated-orcid":false,"given":"Pieter\u2010Jan","family":"De Sutter","sequence":"first","affiliation":[{"name":"Department of Bioanalysis, Faculty of Pharmaceutical Sciences Ghent University  Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7701-289X","authenticated-orcid":false,"given":"Louis","family":"Sandra","sequence":"additional","affiliation":[{"name":"Department of Bioanalysis, Faculty of Pharmaceutical Sciences Ghent University  Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2298-0404","authenticated-orcid":false,"given":"Judith","family":"Van Ovost","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Surgery, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences Ghent 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