| Popis: |
Over the past decade, increasing data have emphasized both the importance of dihydropyrimidine dehydrogenase (DPD), the initial, rate-limiting enzyme in the catabolism of fluorouracil (5-FU), and its role as a control step in 5-FU metabolism, regulating the availability of 5-FU for anabolism. It is now clear that DPD also accounts for much of the variability observed with therapeutic use of 5-FU, including variabilities in 5-FU levels over a 24-hour infusion, interindividual pharmacokinetics, bioavailability, toxicity, and drug response (resistance). This variability makes effective dosing of 5-FU and related drugs difficult. In order to lessen this variability, and potentially improve 5-FU pharmacology, the pharmaceutical industry has made an effort to develop DPD inhibitors to modulate 5-FU metabolism, which has resulted in the creation of a new subclass of orally administered fluoropyrimidines, known as DPD-inhibiting fluoropyrimidines (DIF). Four drugs--uracil and tegafur (UFT) or the combination of UFT and leucovorin, ethynyluracil (eniluracil), S-1, and BOF-A2--have recently undergone clinical evaluation in the United States. The biochemical basis for using these drugs is reviewed. |
