Diagnosis of pyrimidine degradation disorder in patients with severe 5-FU side effect

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18961
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Fujita Health University
• Principal Investigator: NAKAJIMA Yoko 藤田保健衛生大学, 医学部, 助教 (70598309)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: ピリミジン代謝異常症 / 尿中ピリミジン代謝物分析 / 5-フルオロウラシル / 薬物代謝スクスクリーニング / UPLC-MS/MS / DPD酵素活性測定

Outline of Final Research Achievements

Pyrimidine degradation disorder was diagnosed using urine and blood sample from the patients who presented severe 5-FU side effect. Determination of pyrimidine and pyrimidine metabolite in urine was performed by UPLC-MS/MS. The diagnosis of dihydropyrimidine dehydrogenase(DPD) deficiency, dihydropyrimidinase(DHP) deficiency, β-ureidopropionase(βUP) deficiency, was made based on the pattern of the result of pyrimidine metabolite analysis. The stable method of DPD activity in peripheral blood mononuclear cells (PBMC) was established. Decreased DPD activity of 20% of control was detected in the patients with normal urinary pyrimidine metabolite analysis.
Our procedure of screening test for pyrimidine degradation disorders was successfully worked so it is expected to expanding screening test before 5-FU administration.

Free Research Field

先天代謝異常症