Dihydropyrimidine dehydrogenase (DPD) (DPD)

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolic pathway of the pyrimidine bases uracil and thymine, as well as the widely used chemotherapeutic agent 5-fluorouracil (5-FU). Encoded by the DPYD gene, DPD is responsible for metabolizing over 80% of administered 5-FU into inactive metabolites. Genetic variations in DPYD can lead to partial or complete DPD deficiency, which significantly increases the risk of severe, life-threatening toxicities such as myelosuppression and gastrointestinal distress when patients are treated with standard doses of fluoropyrimidines. Consequently, DPD is a critical pharmacogenetic target, with pre-treatment screening for DPYD variants or DPD activity now recommended by several regulatory bodies to guide personalized dosing and improve patient safety. In some therapeutic contexts, DPD inhibitors like gimeracil are co-administered with 5-FU prodrugs to enhance drug exposure and efficacy.

Other names

Dihydropyrimidine deaminaseDihydropyrimidine dehydrogenase [NADP+]Dihydrothymine dehydrogenaseDihydrouracil dehydrogenaseUracil reductaseDPYD

Metabolic inactivation of fluoropyrimidines; Competitive inhibition to increase drug bioavailability