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Pharmacokinetics, a main actor in a many‐sided approach to severe 5‐FU toxicity prediction
Author(s) -
Bocci Guido,
Di Paolo Antonello,
Barbara Cecilia,
Masi Gianluca,
Fornaro Lorenzo,
Loupakis Fotios,
Allegrini Giacomo,
Falcone Alfredo,
Del Tacca Mario,
Danesi Romano
Publication year - 2009
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2008.03307.x
Subject(s) - pharmacokinetics , toxicity , medicine , pharmacology , intensive care medicine
Based on this clinical experience, we detail the principles that should guide the decision-making process regarding the prevention of 5-FU severe toxicity and propose a diagnostic algorithm in order to screen candidate patients to fluoropyrimidine therapy. In the suggested diagnostic algorithm, the predictive 5-FU test dose could be regarded as a triage test, allowing detection of the fraction of patients with normal, impaired or absent fluoropyrimidine metabolism. Other analyses, such as DPD genotyping or even DPD PBMC activity, could be used later as add-on tests and, limited to the still undiagnosed subgroup, to detect those degrees of enzyme activity impairment suitable for possible reduction of 5-FU dose or different treatments. Overall, the published data strongly suggest the use of a diagnostic algorithm based on the sequential application of a 5-FU pharmacokinetic test followed by DPD genotyping and activity in order to make a highly probable diagnosis of altered 5-FU metabolism. Moreover, the application of this model could result in a consistent reduction of costs and morbidity, by limiting genotyping and PBMC DPD activity analysis to only selected subgroups of patients