Etoposide and teniposide are semisynthetic derivatives of podophyllotoxin and are increasingly used in cancer medicine. Teniposide is more highly protein-bound than etoposide, and its uptake and binding to cells is also greater. Etoposide and teniposide are phase-specific cytotoxic drugs acting in the late S and early G2 phases of the cell cycle. They appear to act by causing breaks in DNA via an interaction with DNA topoisomerase II or by the formation of free radicals. Teniposide is more potent as regards the production of DNA damage and cytotoxicity. Most studies show a biexponential decay following intravenous administration of etoposide and teniposide. The terminal elimination half-life of etoposide is less than that of teniposide, and the plasma and renal clearances of etoposide are greater. The peak plasma concentrations of drug and the area under the concentration versus time curve are linearly related to the intravenous dose of both drugs. Considerable interpatient variability of pharmacokinetic parameters exists following intravenous etoposide and teniposide. Various metabolites of etoposide and teniposide have been identified but their detection and quantitation are disputed. Approximately 30 to 70% of a dose of etoposide is accounted for by excretion, whereas the figure appears to be only 5 to 20% for teniposide. The bioavailability of oral etoposide is about 50% but its absorption is not linear with increasing dose within the range in clinical use. There is considerable inter- and intrapatient variability in the pharmacokinetics of oral etoposide. There is no evidence of accumulation of etoposide and teniposide after multiple consecutive doses by the intravenous or oral routes. The exact roles of the liver and kidney in metabolism and excretion of etoposide and teniposide are uncertain. Etoposide has been shown to be a highly schedule-dependent drug in clinical studies. This together with the phase-specific action of etoposide and teniposide and their increasingly widespread use in cancer medicine make the clinical pharmacology of these drugs of great clinical importance.

中文翻译：

---

依托泊苷和替尼泊苷的临床药理作用。

依托泊苷和替尼泊苷是鬼臼毒素的半合成衍生物，并越来越多地用于癌症医学。替尼泊苷比依托泊苷具有更高的蛋白质结合率，并且其摄取和与细胞的结合也更大。依托泊苷和替尼泊苷是在细胞周期的S期晚期和G2期早期起作用的阶段特异性细胞毒性药物。它们似乎是通过与DNA拓扑异构酶II相互作用或通过形成自由基导致DNA断裂而起作用的。就DNA损伤的产生和细胞毒性而言，Teniposide更有效。大多数研究表明，依托泊苷和替尼泊苷静脉给药后双指数衰减。依托泊苷的终末消除半衰期小于替尼泊苷，且依托泊苷的血浆和肾脏清除率更高。药物的峰值血浆浓度以及浓度与时间的关系曲线下的面积与两种药物的静脉内剂量线性相关。静脉注射依托泊苷和替尼泊苷后，患者之间的药代动力学参数存在相当大的差异。已经鉴定出依托泊苷和替尼泊苷的各种代谢物，但其检测和定量存在争议。排泄物占依托泊苷剂量的约30％至70％，而替尼泊苷的数字似乎仅为5％至20％。口服依托泊苷的生物利用度约为50％，但在临床使用范围内，其吸收随着剂量的增加不是线性的。口服依托泊苷的药代动力学在患者之间和患者中存在很大的差异。没有证据表明通过静脉内或口服途径多次连续给药后依托泊苷和替尼泊苷的蓄积。肝和肾在依托泊苷和替尼泊苷的代谢和排泄中的确切作用尚不确定。依托泊苷已被证明是临床研究中高度依赖时间表的药物。依托泊苷和替尼泊苷的阶段特异性作用及其在癌症医学中的越来越广泛的应用，使得这些药物的临床药理学具有重要的临床意义。