Department of Clinical Pharmacy, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, Sichuan, People's Republic of China.
Drug Des Devel Ther. 2022 Nov 14;16:3947-3955. doi: 10.2147/DDDT.S387920. eCollection 2022.
Poly (ADP-ribose) polymerase (PARP) inhibitors are small-molecule inhibitors of PARP enzymes (including PARP1, PARP2, and PARP3) that exhibit activity against tumor cells with defects in DNA repair. In recent years, five PARP inhibitors, olaparib, niraparib, rucaparib, talazoparib and veliparib, have been developed for the treatment of solid tumors, particularly in patients with breast-related cancer antigen (BRCA) 1/2 mutations, or those without a functional homologous recombination repair pathway. These novel treatments exhibit improved efficacy and toxicity when compared to conventional chemotherapy agents. The five PARP inhibitors are eliminated primarily via the liver and kidneys, hepatic or renal impairment may significantly affect their pharmacokinetics (PK). Therefore, it is important to know the effects of hepatic or renal impairment on the PK and safety of PARP inhibitors. In this review, we characterize and summarize the effects of hepatic and renal function on the PK of PARP inhibitors and provide specific recommendations for clinicians when prescribing PARP inhibitors in patients with hepatic or renal impairment.
聚(ADP-核糖)聚合酶(PARP)抑制剂是 PARP 酶(包括 PARP1、PARP2 和 PARP3)的小分子抑制剂,对 DNA 修复缺陷的肿瘤细胞具有活性。近年来,已经开发了五种 PARP 抑制剂,奥拉帕利、尼拉帕利、鲁卡帕利、他拉唑帕利和维利帕利,用于治疗实体瘤,特别是在具有乳腺癌相关癌抗原(BRCA)1/2 突变的患者或那些缺乏功能同源重组修复途径的患者中。与传统化疗药物相比,这些新型治疗方法在疗效和毒性方面都有所提高。五种 PARP 抑制剂主要通过肝脏和肾脏消除,肝或肾功能损害可能会显著影响其药代动力学(PK)。因此,了解肝或肾功能损害对 PARP 抑制剂 PK 和安全性的影响非常重要。在这篇综述中,我们描述并总结了肝肾功能对 PARP 抑制剂 PK 的影响,并为临床医生在肝或肾功能损害患者中开具 PARP 抑制剂时提供了具体建议。