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

• 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
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1080/15257770802145009

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.