How does the determination of plasma endogenous uracil and dihydrouracil levels differ in various clinical settings?
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The determination of plasma endogenous uracil (U) and dihydrouracil (DHU) levels varies across clinical settings. Studies have shown that measuring U plasma concentrations can serve as a surrogate for dihydropyrimidine dehydrogenase (DPD) activity. This is crucial before initiating fluoropyrimidine (FP) chemotherapy to prevent severe toxicity. While traditional methods involve phlebotomy, innovative devices like Tasso-SST® allow for small blood samples from skin capillaries, simplifying the process. Additionally, the correlation between plasma uracil values and DPD deficiency is being explored to optimize treatment balance between efficacy and toxicity. Endogenous U and DHU measurements, adjusted for renal function, have shown promise in predicting severe fluoropyrimidine toxicity, outperforming genotyping for DPYD variants. A bioanalytical method has been developed for simultaneous U and 5-FU determination in plasma, aiding in phenotyping before FP treatment.
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| Papers (5) | Insight |
|---|---|
| The determination of plasma uracil and dihydrouracil levels aids in phenotyping uracil metabolism pre-fluoropyrimidine treatment, enabling toxicity prevention and dose adjustment based on enzyme activity levels. | |
| The study refines pre‐analytical recommendations for measuring uracil and dihydrouracil levels, crucial for reliable dihydropyrimidine dehydrogenase deficiency testing before fluoropyrimidine administration in France. | |
| Not addressed in the paper. | |
| Plasma endogenous uracil and dihydrouracil levels, when adjusted to renal function, can predict severe fluoropyrimidine toxicity risk more effectively than DPYD genotyping but less so than a thymine challenge test. | |
2 Citations | The Tasso-SST® device allows for capillary blood microsampling, correlating well with venous plasma for uracil measurement, offering a convenient alternative for assessing dihydropyrimidine dehydrogenase deficiency. |
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