Laboratoire De Pharmacologie, Institut Claudius-Regaud, IUCT-Oncopole , Toulouse Cedex 9, France.
Cancer Research Center of Toulouse, INSERM UMR1037, Team 14 DIAD (Dose Individualization of Anticancer Drug) , Toulouse, France.
Expert Opin Drug Metab Toxicol. 2020 Oct;16(10):907-925. doi: 10.1080/17425255.2020.1789590. Epub 2020 Oct 5.
: Platinum-derived drugs are commonly used for the treatment of solid tumors. The differences in chemical structures of these molecules lead to different pharmacological properties, in terms of indication, efficacy, and toxicity. Their pharmacokinetics (PK) differ according to their respective renal elimination and have led to many studies investigating their dose optimization. : This review attempts to summarize and compare PK and pharmacodynamics of cisplatin, carboplatin, and oxaliplatin, with an emphasis on differences of dose calculations and opportunities for therapeutic drug monitoring (TDM) in various patient populations. : Although cisplatin and carboplatin can be considered as analogs since they share the same DNA interacting properties, the slower hydrolysis of the latter results in a better safety profile. Carboplatin is the only drug in oncology to be administrated according to a target area under the curve of concentration time, considering that its PK variability is almost fully explained by renal function, not by body size. This enables individual dosing based on predicted carboplatin clearance (along with patients renal characteristics) or on actual clearance with TDM, especially in a high-dose protocol.
铂类药物通常用于治疗实体瘤。这些分子的化学结构差异导致了其在适应证、疗效和毒性方面的不同药理学特性。它们的药代动力学(PK)因各自的肾脏清除率而有所不同,这导致了许多研究探讨了其剂量优化。
本综述试图总结和比较顺铂、卡铂和奥沙利铂的 PK 和药效动力学,重点是在不同患者人群中剂量计算和治疗药物监测(TDM)的差异。
虽然顺铂和卡铂可以被认为是类似物,因为它们具有相同的 DNA 相互作用特性,但后者较慢的水解导致其安全性更好。卡铂是唯一一种根据浓度时间曲线下面积(AUC)目标进行给药的肿瘤学药物,因为其 PK 变异性几乎完全由肾功能而不是身体大小来解释。这使得可以根据预测的卡铂清除率(结合患者的肾脏特征)或通过 TDM 进行实际清除率进行个体化给药,尤其是在高剂量方案中。