Pharmacokinetics of 5-Fluorouracil in Patients Heterozygous for the IVS14+1G > A Mutation in the Dihydropyrimidine Dehydrogenase Gene

5-Fluorouracil (5FU) and capecitabine are two of the most frequently prescribed chemotherapeutic drugs for the treatment of patients with cancer. Administration of test doses of 5FU to eight patients heterozygous for the IVS14+1G > A mutation and five control patients showed that the AUC and clea...

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Bibliographic Details
Published in:Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2008-06, Vol.27 (6-7), p.692-698
Main Authors: van Kuilenburg, A. B. P., Maring, J. G., Schalhorn, A., Terborg, C., Schmalenberg, H., Behnke, D., Schwabe, W., Jabschinsky, K., Hausler, P.
Format: Article
Language:English
Subjects:
5-fluorouracil
Antineoplastic Agents - blood
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - therapeutic use
Area Under Curve
Dihydropyrimidine dehydrogenase
Dihydropyrimidine Dehydrogenase Deficiency
Dihydrouracil Dehydrogenase (NADP) - genetics
DPYD
Fluorouracil - blood
Fluorouracil - pharmacokinetics
Fluorouracil - therapeutic use
Heterozygote
Humans
Metabolic Clearance Rate
Mutation - genetics
Neoplasms - blood
Neoplasms - drug therapy
Neoplasms - enzymology
pharmacokinetics
toxicity
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Summary:5-Fluorouracil (5FU) and capecitabine are two of the most frequently prescribed chemotherapeutic drugs for the treatment of patients with cancer. Administration of test doses of 5FU to eight patients heterozygous for the IVS14+1G > A mutation and five control patients showed that the AUC and clearance were weak parameters with respect to the identification of patients with a DPD deficiency. However, highly significant differences were observed for the terminal half life of 5FU between DPD patients and controls. Thus, a DPD deficiency could be predicted from 5FU blood concentrations measured after the administration of a test dose of 5FU.
ISSN:1525-7770
1532-2335
DOI:10.1080/15257770802145009