An in vitro approach to simulate the process of 5-fluorouracil degradation with dihydropyrimidine dehydrogenase: the process in accordance to the first-order kinetic reaction

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Wei QinPengmei Li

Abstract

Partial or complete deficiency in the dihydropyrimidine dehydrogenase (DPD) has been observed in 3%-5% and 0.1% of the general population, respectively. It causes severe toxicity in the context of 5-fluorouracil (5-FU) therapy. However, the current tests for determination of DPD deficiency have limitations in routine clinical usage.Therefore, an in vitro approach for simulating 5-FU degradation was established by mixing 5-FU with blank whole blood matrix in this study. The effects of initial 5-FU concentrations and temperatures on DPD activities were investigated as well.The degradation process followed the first-order kinetic reaction (r2>0.98). The degradation rates were determined by temperature and individually different. The DPD inhibitor, gimeracil, could block this degradation, which indicated that DPD was the main factor. The degradation process of 5-FU in patients' whole blood in vitro was consistent with it after mixing 5-FU with blank whole blood matrix.In conclusion, mixing 5-FU with blank matrix can simulate the process of 5-FU degradation with DPD.

References

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