氟嘧啶衍生物卡培他滨和5'-脱氧-5-氟尿苷（5'-DFUR）的药代动力学和药效学比较。

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

作者信息

Ebi Hiromichi, Sigeoka Yasushi, Saeki Toshiaki, Kawada Kenji, Igarashi Tadahiko, Usubuchi Noriko, Ueda Ryuzo, Sasaki Yasutsuna, Minami Hironobu

机构信息

Division of Oncology/Hematology, Department of Medicine, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.

出版信息

Cancer Chemother Pharmacol. 2005 Aug;56(2):205-11. doi: 10.1007/s00280-004-0934-7. Epub 2005 Apr 21.

DOI:10.1007/s00280-004-0934-7

PMID:15844007

Abstract

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/m2 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 Cmax of 5'-DFUR tended to be higher in patients with a partial response (3.83 microg h/ml and 4.88 microg/ml) and stable disease (6.46 microg h/ml and 4.96 microg/ml) than in those with disease progression (2.53 microg h/ml and 1.36 microg/ml). The AUC and Cmax of 5'-DFUR was significantly related to overall survival.

CONCLUSIONS

These results support the superiority of capecitabine over 5'-DFUR.

摘要

目的

卡培他滨是一种三步前体药物，其设计初衷是成为中间代谢产物5'-脱氧-5-氟尿苷（5'-DFUR）更有效、更安全的替代品。我们比较了这些药物在转移性乳腺癌患者中的药代动力学/药效学。

方法

6例患者每日两次口服卡培他滨，剂量为1657mg/m²，17例患者每日三次口服5'-DFUR，剂量为400mg。两种药物均给药21天，随后休息7天。

结果

卡培他滨的每日5'-DFUR AUC中位数显著高于5'-DFUR（81.1 vs 32.6 mmol h/l；P = 0.01）。接受5'-DFUR治疗后，部分缓解患者（3.83 microg h/ml和4.88 microg/ml）和疾病稳定患者（6.46 microg h/ml和4.96 microg/ml）的5'-DFUR AUC中位数和Cmax往往高于疾病进展患者（2.53 microg h/ml和1.36 microg/ml）。5'-DFUR的AUC和Cmax与总生存期显著相关。