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dc.creatorFernández-de-Trocóniz, J.I. (José Ignacio)-
dc.creatorParra-Guillen, Z.P. (Zinnia Patricia)-
dc.creatorSchmid, U. (Ulrike)-
dc.creatorJanda, A. (Álvaro)-
dc.creatorFreiwald, M. (Matthias)-
dc.date.accessioned2024-01-17T12:12:34Z-
dc.date.available2024-01-17T12:12:34Z-
dc.date.issued2019-
dc.identifier.citationFernández-de-Trocóniz, J.I. (José Ignacio); Parra-Guillen, Z.P. (Zinnia Patricia). "Model-Informed Dose Selection for Xentuzumab, a Dual Insulin-Like Growth Factor-I/II—Neutralizing Antibody". Clinical Pharmacology & Therapeutics. 107 (3), 2019, 597 - 606es_ES
dc.identifier.urihttps://hdl.handle.net/10171/68396-
dc.description.abstractOver the past decade, the insulin-like growth factor (IGF)-signaling pathway has gained substantial interest as potential therapeutic target in oncology. Xentuzumab, a humanized IgG1 monoclonal antibody, binds to IGF-I and IGF-II thereby inhibiting the downstream signaling essential for survival and tumor growth. This pathway is further regulated by circulating IGF binding proteins (IGFBPs). In this work, a mechanistic model characterizing the dynamics and interactions of IGFs, IGFBPs, and Xentuzumab has been developed to guide dose selection. Therefore, in vitro and in vivo literature information was combined with temporal IGF-I, IGF-II, and IGFBP-3 total plasma concentrations from two phase I studies. Based on the established quantitative framework, the time-course of free IGFs as ultimate drug targets not measured in clinics was predicted. Finally, a dose of 1000 mg/week—predicted to reduce free IGF-I and free IGF-II at steady-state by at least 90% and 64%, respectively—was suggested for phase II.es_ES
dc.language.isoenges_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectInsulin-like growth factor (IGF)es_ES
dc.subjectIgG1 monoclonal antibodyes_ES
dc.subjectBinding proteins (IGFBPs)es_ES
dc.subjectXentuzumabes_ES
dc.subjectIGFBP-3es_ES
dc.subjectIGF-Ies_ES
dc.subjectIGF-IIes_ES
dc.titleModel-Informed Dose Selection for Xentuzumab, a Dual Insulin-Like Growth Factor-I/II—Neutralizing Antibodyes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publisherversionhttps://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.1648es_ES
dadun.citation.endingPage606es_ES
dadun.citation.number3es_ES
dadun.citation.publicationNameClinical Pharmacology & Therapeuticses_ES
dadun.citation.startingPage597es_ES
dadun.citation.volume107es_ES

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