Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Section of Hematology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Pharmacol Res. 2021 May;167:105537. doi: 10.1016/j.phrs.2021.105537. Epub 2021 Mar 6.
Preclinical and clinical investigation on proteasome as a druggable target in cancer has led to the development of proteasome inhibitors (PIs) with different pharmacodynamic and pharmacokinetic properties. For example, carfilzomib has a better safety profile and a lower risk of clinically relevant drug-drug interactions than bortezomib, whereas ixazomib can be orally administered on a weekly basis due to a very long elimination half-life and high systemic exposure. The purpose of this review article is to elucidate the quantitative and qualitative differences in potency, selectivity, pharmacokinetics, safety and drug-drug interactions of clinically validated PIs to provide useful information for their clinical use in real life setting.
在癌症中，蛋白酶体作为一个可药物治疗的靶点的临床前和临床研究已经导致了具有不同药效学和药代动力学特性的蛋白酶体抑制剂（PI）的发展。例如，卡非佐米比硼替佐米具有更好的安全性特征和更低的临床相关药物相互作用风险，而伊沙佐米由于消除半衰期长和全身暴露量高，可以每周口服给药。本文综述的目的是阐明已在临床上验证的 PIs 在效力、选择性、药代动力学、安全性和药物相互作用方面的定量和定性差异，为其在实际临床应用中提供有用的信息。
