Pharmacokinetics of 5-fluorouracil: inter-relationship with biochemical kinetics in monitoring therapy

Clinical Pharmacokinetics
W Sadee, C G Wong

Abstract

The major difficulty in using pharmacokinetic concepts for monitoring individual therapy with 5-fluorouracil is based on the mostly intracellular location of the active nucleotide metabolites of 5-fluorouracil with no clear correlation of plasma levels of the drug. In addition, the basic biochemical mechanism of 'thymine-less cell death' following inhibition of de novo thymidylate synthesis by 2'-deoxy-5-flurouridine 5'-monophosphate (FdUMP) is poorly understood, and only some of the biochemical determinants of therapeutic response to 5-fluorouracil are known. Individualised therapy with 5-fluorouracil requires an intergrated approach which should include methods of pharmacokinetics and biochemical kinetics. 5-Fluorouracil stands as an example for most of the pyrimidine and purine metabolites to which similar consideration apply in monitoring of cancer chemotherapy.

Citations

Jun 1, 1979·British Journal of Clinical Pharmacology·R E FinchA F Lant
Apr 1, 1992·Journal of Pharmacokinetics and Biopharmaceutics·M V St-PierreK S Pang
Sep 1, 1979·British Journal of Clinical Pharmacology·J R Trounce
Dec 1, 1979·Journal of Pharmacokinetics and Biopharmaceutics·B G GustavssonO E Almersjö
May 1, 1980·Acta Pharmacologica Et Toxicologica·O E AlmersjöP Wåhlén
Oct 1, 1988·Journal of Pharmacokinetics and Biopharmaceutics·M V St-PierreK S Pang
Jan 1, 1981·Journal of Cancer Research and Clinical Oncology·B SchultzeW Maurer

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