Altered plasma kinetics of 5-FU at high dosage in rat and man

To provide a model for pharmacokinetic studies in patients administered high iv doses of 5-FU after allopurinol or other modifiers of toxicity, rats were given radioactive 5-FU as an iv bolus. At a dose of 50 mg/m2 only 16% of circulating radioactivity was identified as 5-FU after 30 minutes, wherea...

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Bibliographic Details
Published inCancer treatment reports Vol. 69; no. 1; p. 133
Main Authors Schwartz, P M, Turek, P J, Hyde, C M, Cadman, E C, Handschumacher, R E
Format Journal Article
LanguageEnglish
Published United States 01.01.1985
Subjects
Animals
Female
Fluorouracil - administration & dosage
Fluorouracil - blood
Fluorouracil - therapeutic use
Half-Life
Humans
Injections, Intravenous
Kinetics
Neoplasms - blood
Neoplasms - drug therapy
Rats
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Summary:To provide a model for pharmacokinetic studies in patients administered high iv doses of 5-FU after allopurinol or other modifiers of toxicity, rats were given radioactive 5-FU as an iv bolus. At a dose of 50 mg/m2 only 16% of circulating radioactivity was identified as 5-FU after 30 minutes, whereas greater than 90% of radioactivity was 5-FU when rats were given a 1800-mg/m2 dose. This 36-fold increase in 5-FU dose was associated with a greater than 150-fold increase in the 30-minute plasma concentration of 5-FU (0.02-3.3 mM). In patients, it was possible to increase the maximum tolerated dose of 5-FU given as a weekly rapid iv bolus from 800 to 1700 mg/m2 when a 3-day course of allopurinol (900 mg/day orally) preceded 5-FU administration. A dose-dependent increase in the apparent half-life of 5-FU in the plasma was observed and plasma concentrations at 30 minutes were as high as 500 microM after a 1600-mg/m2 dose of the drug.
ISSN:0361-5960