Dihydropyrimidine deshydrogenase (DPD): rhythm and consequences

Dihydropyrimidine deshydrogenase (DPD) is the rate limiting enzyme of 5-fluorouracil (5-FU) catabolism and its activity is generally determined in peripheral blood mononuclear cells. Several studies have highlighted interactions between toxicities to 5-FU and a DPD activity deficiency. Circadian variations in 5-FU anabolism enzymes are suggested. Circadian variations in 5-FU catabolism enzymes, and especially for DPD in healthy subjects or patients, have shown in some cases circadian variations in DPD activity but with different peak times. Based on this knowledge, chronomodulated therapy for the association 5-FU-folinic acid with maximal delivery rate in the first half of the night was shown clearly to be 5 times less toxic than control flat therapy. Nevertheless, in the most active chronotherapy pattern, 30% of the patients have also toxicities. However the timing of the individual peak-of DPD activity remains controversial. (c) 2005 Publie par Elsevier SAS.