卡培他滨的药理特性及临床应用进展

卡培他滨 (capecitabine)是一种极具潜力的选择性肿瘤内激活的口服氟尿嘧啶氨基甲酸酯类抗肿瘤药物 ,它通过肝脏和肿瘤内的 3种酶转化为氟尿嘧啶 (FU)。本品口服后完整地通过胃肠壁 ,首先经肝脏羧酸酯酶催化代谢为 5’ 脱氧 5 氟胞苷 (5’ deoxy 5 fluorocytidine,5’ DFCR) ,然后经肝脏和肿瘤细胞中的胞苷脱氨酶催化转化为 5’ 脱氧 氟尿嘧啶 (5’ deoxy 5 fluorouridine,5’ DFUR) ,最后经胸苷磷酸化酶 (thymidinephosphorylase,TP)催化转化为氟尿嘧啶 (FU)而发挥细胞毒作用。卡培他滨临床用于晚期转移性乳腺癌 ,结、直肠癌以及其他实体瘤的治疗 ,具有良好的抗肿瘤作用和极少的不良反应。本文主要对卡培他滨的药理作用特性、药动学和临床应用进展等作一综述。

Pharmacology and clinical use of cepecitabine

Capecitabine is a novel, oral, selectively tumor activated fluoropyrimidine carbamate with antineoplastic activity. That is converted to 5 fluorouracil (5 FU) by three enzymes located in the liver and tumors. Capecitabine passes intact through the intestinal tract after oral administration and is metabolized via a 3 step process to the active agent 5 FU. The first step is the conversion to 5’ deoxy 5 fluorocytidine (5’ DFCR) by carboxylesterase located in the liver, then to 5’ deoxy 5 fluorouridine (5’ DFUR) by cytidine deaminase highly expressed in the liver and varous solid tumors, and finally to 5 FU by thymidine phasphorylase (dThdPase) preferentially located in tumor tissues. Capecitabine was rationally designed to improve antitumor activity and reduce toxicity, and was used clinically for the treatment of advanced metastatic breast cancer, colorectal cancer and other solid tumors. In this paper, the mechanism of actions, pharmacokinetics and clinical use were reviewed.