Pharmacokinetic and pharmacodynamic comparison of fluoropyrimidine derivatives, capecitabine and 5′-deoxy-5-fluorouridine (5′-DFUR)

Purpose: Capecitabine is a three-step prodrug that was rationally designed to be a more effective and safer alternative to its intermediate metabolite, 5′-deoxy-5-fluorouridine (5′-DFUR). We compared the pharmacokinetics/pharmacodynamics of these drugs in metastatic breast cancer patients. Methods: Six patients received oral capecitabine at 1657 mg/m ² twice daily and 17 received 5′-DFUR at 400 mg three times daily. Both drugs were administered for 21 days followed by a 7-day rest. Results: Median daily 5′-DFUR AUC was significantly higher for capecitabine than for 5′-DFUR (81.1 vs 32.6 mmol h/l; P=0.01). Following treatment with 5′-DFUR, the median AUC and C_max of 5′-DFUR tended to be higher in patients with a partial response (3.83 μg h/ml and 4.88 μg/ml) and stable disease (6.46 μg h/ml and 4.96 μg/ml) than in those with disease progression (2.53 μg h/ml and 1.36 μg/ml). The AUC and C_max of 5′-DFUR was significantly related to overall survival. Conclusions: These results support the superiority of capecitabine over 5′-DFUR.