2000 Fiscal Year Final Research Report Summary
Possible prediction to fluorouracil (5-FU) anti-cancer agent -Studies of urinary pyrimidine levels in the cancer patients and 5-FU pharmacokinetics in the patients with cancer.
| Project/Area Number |
10672154
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Jichi Medical School |
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Principal Investigator |
TOKUE Akihiko Faculty of Medicine, Jichi Medical School, Professor, 医学部, 教授 (80049022)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Eiji Faculty of Medicine, Jichi Medical School, Associate Professor, 医学部, 助教授 (00245044)
FUJIMURA Akio Faculty of Medicine, Jichi Medical School, Professor, 医学部, 教授 (90156901)
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| Project Period (FY) |
1998 – 2000
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| Keywords | 5-fluorouracil / urinary uracil / urinary dihydrouracil / pharmacokinetics / reference range / dihydropyrimidine dehydrogenase |
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| Research Abstract |
Insufficiency of dihydropyrimidine dehydrogenase or dihydropyrimidinase, enzymes that catalyze the breakdown of pyrimidine chemotherapy agents such as 5-fluorouracil, may cause serious adverse reactions to these agents. We attempted to establish the reference range for urinary pyrimidines in the 10 cancer patients (8 gastric cancer, and 2 renal carcinoma) to detect individuals with abnormal pyrimidine metabolism. Urinary dihydrouracil and uracil levels were determined by high-performance liquid chromatography with column switching. The concentrations of 5-FU were significantly different among each patients (T max ; 5 to 10 min, C max ; 102.9 to 1121 ng/ml, and AUC ; 1820 to 11381 ng/ml.min). Especially, in the patients with gastric cancer, 5-FU concentrations was markedly increased from prioperative to postoperative stage. To evaluate the influence of gastrectomy on absorption, the changes in blood levels of 5-FU preparations before after gastrectomy were comparatively studied in the rat. The greatest influence was given to 5-FU dry syrup ; to the peak level in blood was shortened after operation, and the distributed amount to blood was about 10 times that before operation.
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Research Products
(8 results)
