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Fluorouracil is used clinically against a variety of solid tumors. It is a prodrug that undergoes a series of intracellular conversions to active cytotoxic species. There is wide interindividual variability in fluorouracil metabolism; furthermore, it has nonlinear kinetics that make it relatively more difficult to predict plasma concentrations after brief infusions compared with prolonged infusions. There is an increasing body of evidence that relates plasma fluorouracil concentrations to toxicity and effectiveness, and consequently there may be a definable mathematical relationship that describes a 'therapeutic window'. Dose nomograms and pharmacokinetic models based on limited sampling strategies have been developed, as have empirical dose escalation schedules based on multivariate analysis of the determinants of toxicity, The utility of these approaches should be tested in properly powered, prospective, randomised trials.

Original publication

DOI

10.2165/00003088-199936060-00001

Type

Journal article

Journal

Clin Pharmacokinet

Publication Date

06/1999

Volume

36

Pages

391 - 398

Keywords

Age Factors, Antimetabolites, Antineoplastic, Dose-Response Relationship, Drug, Drug Monitoring, Female, Fluorouracil, Humans, Infusions, Intravenous, Male, Neoplasms, Randomized Controlled Trials as Topic, Sex Factors