Читать книгу Transporters and Drug-Metabolizing Enzymes in Drug Toxicity - Albert P. Li - Страница 79

Toxicity observed in patients coadministered SRV and 5‐FU prodrugs is a result of unexpected elevation of plasma 5‐FU levels. The toxicity observed included bone marrow damage, intestinal membrane mucosa atrophy, decreases in white blood cells and platelets, diarrhea with bloody flux, and severe anorexia. Both laboratory animal and clinical results confirm that SRV is metabolized by intestinal flora to (E)‐5‐(2‐bromovinyl)uracil (BVU), a suicide inhibitor of dihydropyrimidine dehydrogenase (DPD), the key enzyme for 5‐FU metabolism and elimination, leading to retardation of 5‐FU metabolic clearance, resulting in its accumulation to toxic levels [166–168] (Figure 3.1).

Figure 3.1 Chemical structure of the 12 toxic drugs reviewed.