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: André Bp van Kuilenburg, Jan Gerard Maring
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 14 Issue 7 Pg. 799-811 (May 2013) ISSN: 1744-8042 [Electronic] England
• PMID: 23651027 (Publication Type: Journal Article, Review)

Chemical References

• Antimetabolites, Antineoplastic
• Dihydrouracil Dehydrogenase (NADP)
• Fluorouracil

Topics

• Antimetabolites, Antineoplastic (administration & dosage, pharmacokinetics)
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Dihydropyrimidine Dehydrogenase Deficiency (metabolism)
• Dihydrouracil Dehydrogenase (NADP) (metabolism)
• Drug Monitoring (methods)
• Fluorouracil (administration & dosage, pharmacokinetics)
• Humans
• Neoplasms (drug therapy, metabolism)