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Pharmacokinetics of 5-Fluorouracil in Patients Heterozygous for the IVS14+1G > A Mutation in the Dihydropyrimidine Dehydrogenase Gene |
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| Authors: | A B P van Kuilenburg J G Maring A Schalhorn C Terborg H Schmalenberg D Behnke |
| Institution: | 1. Academic Medical Center , University of Amsterdam, Emma Children's Hospital and Department of Clinical Chemistry , Amsterdam, The Netherlands;2. Diaconessen Hospital Meppel and Bethesda Hospital Hoogeveen, Department of Pharmacy, Hoogeveenseweg , Meppel, The Netherlands;3. Med. Klinik III , University Hospital Gro?hadern , Munich, Germany;4. Department of Neurology , University Hospital of Jena , Jena, Germany;5. Klinik und Poliklinik für Innere Medizin II , University Hospital of Jena , Jena, Germany;6. Department of Research and Development , Oncoscreen GmbH. , Jena, Germany |
| Abstract: | 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. |
| Keywords: | Dihydropyrimidine dehydrogenase 5-fluorouracil DPYD pharmacokinetics toxicity |