{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:50:06Z","timestamp":1788915006511,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,11,20]],"date-time":"2021-11-20T00:00:00Z","timestamp":1637366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Liposomal irinotecan is a liposomal formulation of irinotecan, which prolongs circulation of irinotecan and its active metabolite SN\u201038. A population pharmacokinetic (PK) model was developed based on data from seven studies (<jats:italic>N<\/jats:italic>\u00a0=\u00a0440). Adequacy of the model was assessed using multiple methods, including visual predictive check. Associations between PK exposure and the incidence of diarrhea (grade \u22653) and neutropenia adverse events (AEs) (grade \u22653) at first event in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) were investigated using logistic regression based on data from two studies (the phase III NAPOLI\u20101 [<jats:italic>N<\/jats:italic>\u00a0=\u00a0260] and phase I\/II NCT02551991 [<jats:italic>N<\/jats:italic>\u00a0=\u00a056] trials). The PKs of total irinotecan was described by a two\u2010compartment model with first\u2010order elimination, with SN\u201038 formed directly by a first\u2010order constant from the central compartment of irinotecan or after using a transit compartment. Clearance was 17.9\u00a0L\/week (0.107\u00a0L\/h) and 19,800\u00a0L\/week (118\u00a0L\/h) for total irinotecan and SN\u201038, respectively. The UGT1A1*28 7\/7 homozygous genotype had no significant impact on SN\u201038 clearance. Model evaluation was satisfactory for both irinotecan and SN\u201038. The incidence of diarrhea (grade \u22653) at first event was significantly higher with increasing average concentrations of total irinotecan and SN\u201038; there was no significant association between an increased risk of neutropenia AEs (grade \u22653) at first event and average SN\u201038 concentrations. In summary, the PKs of total irinotecan and SN\u201038 after administration of liposomal irinotecan were well\u2010described by the model. The UGT1A1*28 status had no significant impact on the PKs of liposomal irinotecan.<\/jats:p>","DOI":"10.1002\/psp4.12725","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T07:30:56Z","timestamp":1636443056000},"page":"1550-1563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Population pharmacokinetics of liposomal irinotecan in patients with cancer and exposure\u2013safety analyses in patients with metastatic pancreatic cancer"],"prefix":"10.1002","volume":"10","author":[{"given":"Karl","family":"Brendel","sequence":"first","affiliation":[{"name":"Ipsen Les\u2010Ulis France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanios","family":"Bekaii\u2010Saab","sequence":"additional","affiliation":[{"name":"Mayo Clinic Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M","family":"Boland","sequence":"additional","affiliation":[{"name":"Roswell Park Cancer Institute Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farshid","family":"Dayyani","sequence":"additional","affiliation":[{"name":"University of California Irvine Orange California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Dean","sequence":"additional","affiliation":[{"name":"St John of God Hospital Subiaco Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Macarulla","sequence":"additional","affiliation":[{"name":"Vall d\u00b4Hebr\u00f3n University Hospital Vall d\u00b4Hebr\u00f3n Institute of Oncology Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Ipsen Abingdon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kabir","family":"Mody","sequence":"additional","affiliation":[{"name":"Mayo Clinic Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pedret\u2010Dunn","sequence":"additional","affiliation":[{"name":"Ipsen Abingdon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zev A","family":"Wainberg","sequence":"additional","affiliation":[{"name":"Ronald Regan UCLA Medical Center Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ipsen Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dju011"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv295"},{"key":"e_1_2_9_5_1","unstructured":"National Comprehensive Cancer Network.Pancreatic adenocarcinoma version 2.2021.2020.https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/pancreatic.pdf. 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