Department of Pharmacy, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA.
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
Clin Pharmacokinet. 2017 Nov;56(11):1255-1266. doi: 10.1007/s40262-017-0529-1.
Management of chronic lymphocytic leukemia has changed markedly over the last several years with the emergence of several novel oral agents targeting B-cell receptor and Bcl-2 signaling pathways. For patients requiring treatment, ibrutinib, idelalisib, and venetoclax offer unique clinical benefits with a different set of therapeutic considerations compared with traditional parenteral therapy. Despite the conveniences afforded by oral therapy, these agents also carry unique logistical obstacles. Drug interactions with agents that are metabolized via the cytochrome P450 3A4 pathway are possible with all three agents. Unique treatment-related adverse events including bleeding and atrial fibrillation with ibrutinib, hepatotoxicity with idelalisib, and tumor lysis syndrome with venetoclax can be severe and dose limiting. Furthermore, dose adjustments for organ dysfunction may also be warranted. Here, we review the available literature on the pharmacokinetic and pharmacodynamic properties of these novel agents to guide the reader in the appropriate use of ibrutinib, idelalisib, and venetoclax.
近年来，随着靶向 B 细胞受体和 Bcl-2 信号通路的新型口服药物的出现，慢性淋巴细胞白血病的治疗发生了显著变化。对于需要治疗的患者，与传统的注射治疗相比，伊布替尼、idelalisib 和 venetoclax 具有独特的临床获益，并需要考虑不同的治疗方案。尽管口服治疗具有便利，但这些药物也存在独特的物流障碍。所有三种药物都可能与经细胞色素 P450 3A4 途径代谢的药物发生药物相互作用。伊布替尼可导致独特的治疗相关不良反应，包括出血和心房颤动；idelalisib 可导致肝毒性；venetoclax 可导致肿瘤溶解综合征，这些不良反应可能很严重，限制剂量。此外，还可能需要针对器官功能障碍进行剂量调整。在此，我们回顾了这些新型药物的药代动力学和药效学特性的相关文献，以指导读者正确使用伊布替尼、idelalisib 和 venetoclax。
