| 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 (2000) Faculty of Medicine, Jichi Medical School, Professor, 医学部, 教授 (80049022)
原田 和博 (1998-1999) 自治医科大学, 医学部, 講師 (70245059)
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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)
徳江 章彦 自治医科大学, 医学部, 教授 (80049022)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
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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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