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The primary aim of this study was to develop a pharmacokinetic model for capecitabine and its metabolites, 5\u2032\u2010deoxy\u20105\u2010fluorocytidine (dFCR), 5\u2032\u2010deoxy\u20105\u2010fluorouridine (dFUR), 5\u2010FU, and fluoro\u2010\u03b2\u2010alanine (FBAL) using data from a heterogeneous population of cancer patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a0237) who participated in seven clinical studies. A four\u2010transit model adequately described capecitabine absorption. Capecitabine, dFCR, and FBAL pharmacokinetics were well described by two\u2010compartment models, and dFUR and 5\u2010FU were subject to flip\u2010flop pharmacokinetics. Partial and total gastrectomy were associated with a significantly faster capecitabine absorption resulting in higher capecitabine and metabolite peak concentrations. Patients who were heterozygous polymorphic for a genetic mutation encoding dihydropyrimidine dehydrogenase, the <jats:italic>DPYD<\/jats:italic>*2A mutation, demonstrated a 21.5% (relative standard error 11.2%) reduction in 5\u2010FU elimination. This comprehensive population model gives an extensive overview of capecitabine and metabolite pharmacokinetics in a large and heterogeneous population of cancer patients.<\/jats:p>","DOI":"10.1002\/psp4.12474","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T14:29:34Z","timestamp":1572013774000},"page":"940-950","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Pharmacokinetics of Capecitabine and Four Metabolites in a Heterogeneous Population of Cancer Patients: A Comprehensive Analysis"],"prefix":"10.1002","volume":"8","author":[{"given":"Bart A.W.","family":"Jacobs","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology The Netherlands Cancer Institute Amsterdam The Netherlands"},{"name":"Department of Pharmacy &amp; Pharmacology The Netherlands Cancer Institute Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten J.","family":"Deenen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Catharina Hospital Eindhoven The Netherlands"},{"name":"Department of Clinical Pharmacology and Toxicology Leiden University Medical Centre Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Joerger","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology The Netherlands Cancer Institute Amsterdam The Netherlands"},{"name":"Department of Pharmacy &amp; 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