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Using an individual patient data model-based meta-analysis (IPD-MBMA) approach, this study aims to build a generalized model by combining IPD from multiple studies, investigating the role of lean body mass (LBM) in 5-FU PK, and exploring a model informed precision dosing (MIPD)-based approach for refining its therapeutic drug monitoring (TDM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Raw PK data from three 5-FU PK studies (726 patients, 2,332 plasma concentrations) were harmonized and grouped into one homogeneous dataset, preserving traceability to the original data source. An overall population PK (popPK) model for intravenous 5-FU was developed using nonlinear mixed-effects modeling (NONMEM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A two-compartment model with both saturable (Michaelis-Menten elimination; V\n                      <jats:sub>max<\/jats:sub>\n                      , K\n                      <jats:sub>m<\/jats:sub>\n                      ) and linear elimination (CL) best described 5-FU disposition, with a stratified error model to capture between-study differences. Body-surface area (BSA) significantly impacted CL, and V\n                      <jats:sub>max<\/jats:sub>\n                      was 15% lower in women and decreased with age. In a parallel analysis, the sex effect on V\n                      <jats:sub>max<\/jats:sub>\n                      was translated into an LBM effect, with metabolic capacity increasing with LBM. Based on a 12-cycle simulation, after 4 cycles of TDM-based dose adjustment, 95% of the patient should be optimally exposed in the context of colorectal cancer (area under the curve, AUC 20\u201329\u00a0mg\u2219h\/L). A virtual MIPD-based approach predicted higher target attainment after one adjustment (70\u2009\u2212\u200968%) compared to classic TDM predictions (49\u201359%) in men and women, respectively. Finally, the administration of a bolus before the continuous infusion of 5-FU is not expected to materially affect its subsequent continuous infusion AUC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Aggregating IPD enables building more generalizable popPK models while accommodating study-specific residual variability; broader raw-data sharing would strengthen current evidence and reveal remaining gaps. For 5-FU, BSA dosing leaves substantial interpatient variability, so LBM-based and model-informed strategies, including\n                      <jats:italic>a priori<\/jats:italic>\n                      dosing and MIPD-assisted TDM, warrant prospective evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00280-026-04885-x","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T07:35:27Z","timestamp":1781249727000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Model-based meta-analysis of individual patient data for the characterization of intravenous 5-fluorouracil population pharmacokinetics"],"prefix":"10.1007","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6334-5565","authenticated-orcid":false,"given":"Myriam","family":"Briki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-4277","authenticated-orcid":false,"given":"Paul","family":"Thoueille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6602-6287","authenticated-orcid":false,"given":"Markus","family":"Joerger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-9096","authenticated-orcid":false,"given":"Etienne","family":"Chatelut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0645-8934","authenticated-orcid":false,"given":"Marylise","family":"Sterle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3132-7730","authenticated-orcid":false,"given":"Antonin","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4728-7013","authenticated-orcid":false,"given":"Anna Dorothea","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0639-5536","authenticated-orcid":false,"given":"Thierry","family":"Buclin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0404-7917","authenticated-orcid":false,"given":"Sandro","family":"Carrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-9317","authenticated-orcid":false,"given":"Monia","family":"Guidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"4885_CR1","doi-asserted-by":"publisher","first-page":"2815","DOI":"10.1200\/JCO.2012.43.4233","volume":"30","author":"JL Marshall","year":"2012","unstructured":"Marshall JL (2012) Maximum-tolerated dose, optimum biologic dose, or optimum clinical value: dosing determination of cancer therapies. 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