Samenvatting
Capecitabine is an oral prodrug of the anticancer drug 5-fluorouracil (5-FU). The primary aim of this study was to develop a pharmacokinetic model for capecitabine and its metabolites, 5′-deoxy-5-fluorocytidine (dFCR), 5′-deoxy-5-fluorouridine (dFUR), 5-FU, and fluoro-β-alanine (FBAL) using data from a heterogeneous population of cancer patients (n = 237) who participated in seven clinical studies. A four-transit model adequately described capecitabine absorption. Capecitabine, dFCR, and FBAL pharmacokinetics were well described by two-compartment models, and dFUR and 5-FU were subject to flip-flop 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 DPYD*2A mutation, demonstrated a 21.5% (relative standard error 11.2%) reduction in 5-FU elimination. This comprehensive population model gives an extensive overview of capecitabine and metabolite pharmacokinetics in a large and heterogeneous population of cancer patients.
Originele taal-2 | Engels |
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Pagina's (van-tot) | 940-950 |
Aantal pagina's | 11 |
Tijdschrift | CPT: Pharmacometrics and Systems Pharmacology |
Volume | 8 |
Nummer van het tijdschrift | 12 |
DOI's | |
Status | Gepubliceerd - 1 dec. 2019 |
Extern gepubliceerd | Ja |