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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorBrendel, Karl
dc.contributor.authorBekaii-Saab, Tanios S
dc.contributor.authorBoland, Patrick M
dc.contributor.authorDayyani, Farshid
dc.contributor.authorDean, Andrew
dc.contributor.authorMacarulla Mercadé, Teresa
dc.date.accessioned2022-05-30T13:22:40Z
dc.date.available2022-05-30T13:22:40Z
dc.date.issued2021-12
dc.identifier.citationBrendel K, Bekaii-Saab T, Boland PM, Dayyani F, Dean A, Macarulla T, et al. Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer and Exposure–Safety Analyses in Patients With Metastatic Pancreatic Cancer. CPT Pharmacometrics Syst Pharmacol. 2021 Dec;10(12):1550–63.
dc.identifier.issn2163-8306
dc.identifier.urihttp://hdl.handle.net/11351/7583
dc.descriptionPharmacokinetics; Liposomal irinotecan; Safety
dc.description.abstractLiposomal irinotecan is a liposomal formulation of irinotecan, which prolongs circulation of irinotecan and its active metabolite SN-38. A population pharmacokinetic (PK) model was developed based on data from seven studies (N = 440). Adequacy of the model was assessed using multiple methods, including visual predictive check. Associations between PK exposure and the incidence of diarrhea (grade ≥3) and neutropenia adverse events (AEs) (grade ≥3) 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-1 [N = 260] and phase I/II NCT02551991 [N = 56] trials). The PKs of total irinotecan was described by a two-compartment model with first-order elimination, with SN-38 formed directly by a first-order constant from the central compartment of irinotecan or after using a transit compartment. Clearance was 17.9 L/week (0.107 L/h) and 19,800 L/week (118 L/h) for total irinotecan and SN-38, respectively. The UGT1A1*28 7/7 homozygous genotype had no significant impact on SN-38 clearance. Model evaluation was satisfactory for both irinotecan and SN-38. The incidence of diarrhea (grade ≥3) at first event was significantly higher with increasing average concentrations of total irinotecan and SN-38; there was no significant association between an increased risk of neutropenia AEs (grade ≥3) at first event and average SN-38 concentrations. In summary, the PKs of total irinotecan and SN-38 after administration of liposomal irinotecan were well-described by the model. The UGT1A1*28 status had no significant impact on the PKs of liposomal irinotecan.
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofseriesCPT: Pharmacometrics & Systems Pharmacology;10(12)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectPàncrees - Càncer - Tractament
dc.subjectMedicaments antineoplàstics - Farmacocinètica
dc.subjectMetàstasi
dc.subject.meshPancreatic Neoplasms
dc.subject.mesh/drug therapy
dc.subject.meshAntineoplastic Agents
dc.subject.mesh/pharmacokinetics
dc.titlePopulation pharmacokinetics of liposomal irinotecan in patients with cancer and exposure–safety analyses in patients with metastatic pancreatic cancer
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1002/psp4.12725
dc.subject.decsneoplasias pancreáticas
dc.subject.decs/farmacoterapia
dc.subject.decsantineoplásicos
dc.subject.decs/farmacocinética
dc.relation.publishversionhttps://doi.org/10.1002/psp4.12725 SECTIONS
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Brendel K] Ipsen, Les-Ulis, France. [Bekaii-Saab T] Mayo Clinic, Phoenix, Arizona, USA. [Boland PM] Roswell Park Cancer Institute, Buffalo, New York, USA. [Dayyani F] University of California Irvine, Orange, California, USA. [Dean A] St John of God Hospital Subiaco, Perth, Western Australia, Australia. [Macarulla T] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
dc.identifier.pmid34750990
dc.identifier.wos000720681300001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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