Pharmacokinetics of 5-FluorouracilInter-relationship with Biochemical Kinetics in Monitoring Therapy
作者:
W. Sadee,
C. G. Wong,
期刊:
Clinical Pharmacokinetics
(ADIS Available online 1977)
卷期:
Volume 2,
issue 6
页码: 437-450
ISSN:0312-5963
年代: 1977
出版商: ADIS
数据来源: ADIS
摘要:
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 to 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-fluorouridine 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 integrated 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 considerations apply in monitoring of cancer chemotherapy.
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