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Can pharmacokinetic monitoring improve clinical use of fluorouracil?
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Young, Annie M., Daryanani, Sunil and Kerr, David J. (1999) Can pharmacokinetic monitoring improve clinical use of fluorouracil? Clinical Pharmacokinetics, 36 (6). pp. 391-398. doi:10.2165/00003088-199936060-00001 ISSN 0312-5963.
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Official URL: http://dx.doi.org/10.2165/00003088-199936060-00001
Abstract
Fluorouracil is used clinically against a variety of solid tumours. 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.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine > R Medicine (General) | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Clinical Pharmacokinetics | ||||
Publisher: | Spring New York LLC | ||||
ISSN: | 0312-5963 | ||||
Official Date: | 1 June 1999 | ||||
Dates: |
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Volume: | 36 | ||||
Number: | 6 | ||||
Page Range: | pp. 391-398 | ||||
DOI: | 10.2165/00003088-199936060-00001 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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