title: Evaluation of 5-fluorouracil pharmacokinetic models and therapeutic drug monitoring in cancer patients.
abstract: 5-fluorouracil (5-FU) remains the cornerstone of all currently applied regimens for the treatment of patients with cancers of the gastrointestinal tract, breast, and head and neck. Unfortunately, a large variation in the clearance of 5-FU has been observed between patients, suggesting that some patients might receive nonoptimal 5-FU doses. However, therapeutic drug monitoring of 5-FU has been shown to result in reduced intra- and inter-individual variability in 5-FU plasma levels and pharmacokinetically guided dose adjustments of 5-FU-containing therapy results in a significantly improved efficacy and tolerability. To date, compartmental Michaelis-Menten elimination-based modeling has proven to be a sensitive and accurate tool for analyzing the pharmacokinetics of 5-FU and to identify patients with a dihydropyrimidine dehydrogenase deficiency. These Michaelis-Menten models also allow the use of a limited sampling strategy and offer the opportunity to predict a priori the 5-FU plasma concentrations in patients receiving adapted doses of 5-FU.
authors: Academic Medical Center, University of Amsterdam, Emma Children's Hospital & Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, F0-220, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. a.b.vankuilenburg@amc.uva.nl
authors: André Bp
authors: AB
authors: van Kuilenburg
authors: Jan Gerard
authors: JG
authors: Maring
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D054067:Dihydropyrimidine Dehydrogenase Deficiency / Q000378:metabolism; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil