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A translational system toxicology model for GI AEs using citrulline was then developed based on new experimental data and parameters from a literature intestinal cell dynamic model. With the addition of feedback\u2010development and tolerance\u2010development mechanisms, the model well captured the plasma citrulline profiles after irinotecan treatment in rats. Subsequently, the model was translated to humans and predicted the observed GI AE dynamics in humans including dose\u2010scheduling effect using the cytotoxic and feedback parameters estimated in rats with slight calibrations. This translational toxicology model could be used for other antineoplastic drugs to simulate various clinical dosing scenarios before human studies and mitigate potential GI AEs.<\/jats:p>","DOI":"10.1002\/psp4.12475","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T18:41:08Z","timestamp":1572547268000},"page":"951-961","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Citrulline\u2010Based Translational Population System Toxicology Model for Gastrointestinal\u2010Related Adverse Events Associated With Anticancer Treatments"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2207-3505","authenticated-orcid":false,"given":"Tomoki","family":"Yoneyama","sequence":"first","affiliation":[{"name":"Quantitative Translational Sciences Takeda Pharmaceuticals International Co. 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