Storniolo A M, Allerheiligen S R, Pearce H L
Department of Cancer Research and Clinical Investigations, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Semin Oncol. 1997 Apr;24(2 Suppl 7):S7-2-S7-7.
Gemcitabine (2',2'-difluorodeoxycytidine) is a novel nucleoside analogue that exerts its antitumor activity via multiple mechanisms of action. These include (1) incorporation of gemcitabine into replicating DNA, which inhibits DNA replication and cell growth, (2) masked DNA chain termination, and (3) several self-potentiation mechanisms that serve to increase intracellular levels of the active compound. Preclinical experiments in various cell lines and animal models demonstrate a broad range of cytotoxic activity. Pharmacokinetic studies of gemcitabine delivered by its usual schedule (30-minute weekly infusion) reveal a short plasma half-life and a high clearance into central and peripheral compartments (two-compartment model). The drug is excreted almost completely in the urine as the parent compound and primary metabolite (difluorodeoxyuridine). Phase I trials demonstrate that pharmacokinetics are schedule dependent and that, in general, gemcitabine is well tolerated. Dose-limiting toxicities are primarily myelosuppression, with other toxicities being rash, flu-like symptoms, and transient elevations in liver function tests.
吉西他滨（2'，2'-二氟脱氧胞苷）是一种新型核苷类似物，通过多种作用机制发挥其抗肿瘤活性。这些机制包括：（1）吉西他滨掺入正在复制的DNA中，从而抑制DNA复制和细胞生长；（2）隐蔽性DNA链终止；（3）几种自身增效机制，这些机制可提高活性化合物的细胞内水平。在各种细胞系和动物模型中进行的临床前实验表明其具有广泛的细胞毒性活性。按照常规给药方案（每周输注30分钟）给予吉西他滨的药代动力学研究显示，其血浆半衰期较短，在中央和外周室（二室模型）中的清除率较高。该药物几乎完全以母体化合物和主要代谢产物（二氟脱氧尿苷）的形式经尿液排泄。I期试验表明，药代动力学取决于给药方案，并且一般来说，吉西他滨耐受性良好。剂量限制性毒性主要是骨髓抑制，其他毒性包括皮疹、流感样症状和肝功能检查结果短暂升高。
