DPDcreatinine

DPDcreatinine is a biomarker used to assess dihydropyrimidine dehydrogenase (DPD) activity by measuring urine-based metabolites normalized to creatinine. The concept centers on the role of DPD as the rate-limiting enzyme in the catabolism of pyrimidines, including uracil and thymine, and its influence on the metabolism of fluoropyrimidine chemotherapy agents such as 5-fluorouracil and capecitabine. Lower DPD activity can lead to higher systemic exposure and a greater risk of severe and sometimes life-threatening toxicity.

Measurement typically involves quantifying pyrimidine metabolites, such as uracil and dihydrouracil, in urine and adjusting the results for creatinine concentration to account for urine dilution. The resulting creatinine-adjusted values (the DPDcreatinine index) are interpreted in the context of local reference ranges and assay methods. In practice, DPDcreatinine is used to complement other assessments of DPD status, including DPYD genotyping and other phenotyping approaches, to inform dosing decisions for fluoropyrimidine therapy.

Interpretation of DPDcreatinine values is nuanced. Abnormally low DPDcreatinine indices may indicate reduced DPD activity and a higher risk of toxicity, potentially guiding dose modification or alternative treatments. However, results can be influenced by kidney function, hydration status, timing of sample collection, and laboratory methodology. Because standardization and clinical validation are still evolving, DPDcreatinine is typically used as part of a broader pharmacogenetic and pharmacokinetic assessment rather than as a sole determinant of therapy.

See also: dihydropyrimidine dehydrogenase, DPYD, fluoropyrimidine toxicity, pharmacogenomics, uracil-to-creatinine ratio.