{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T22:09:26Z","timestamp":1779401366885,"version":"3.53.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"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":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peritoneal metastases (PM) are common in patients with colorectal cancer. Patients with PM have a poor prognosis, and for those who are not eligible for cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), palliative chemotherapy is currently the only option. Recently, we conducted a phase I trial (INTERACT) in which irinotecan was administered intraperitoneally (IP) to 18 patients ineligible for CRS\u2010HIPEC. The primary objective was to evaluate covariates influencing the PK profile of irinotecan and SN\u201038 after IP administration. Secondly, a population PK model was developed to support the further development of IP irinotecan by improving dosing in patients with PM. Patients were treated with IP irinotecan every 2\u2009weeks in combination with systemic FOLFOX\u2010bevacizumab. Irinotecan and SN\u201038 were measured in plasma (588 samples) and SN\u201038 was measured in peritoneal fluid (267 samples). Concentration\u2010Time data were log\u2010transformed and analyzed using NONMEM version 7.5 using FOCE+I estimation. An additive error model described the residual error, with inter\u2010individual variability in PK parameters modeled exponentially. The final structural model consisted of five compartments. Weight was identified as a covariate influencing the SN\u201038 plasma volume of distribution and GGT was found to influence the SN\u201038 plasma clearance. This population PK model adequately described the irinotecan and SN\u201038 in plasma after IP administration, with weight and GGT as predictive factors. Irinotecan is converted intraperitoneal to SN\u201038 by carboxylesterases and the plasma bioavailability of irinotecan is low. This model will be used for the further clinical development of IP irinotecan by providing dosing strategies.<\/jats:p>","DOI":"10.1002\/psp4.13136","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T05:43:37Z","timestamp":1713419017000},"page":"1006-1016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Population pharmacokinetics of intraperitoneal irinotecan and SN\u201038 in patients with peritoneal metastases from colorectal origin"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6039-8458","authenticated-orcid":false,"given":"Pascale C. 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