Salvini Marco, Troia Rossella, Giudice Davide, Pautasso Chiara, Boccadoro Mario, Larocca Alessandra
a Myeloma Unit, Division of Hematology , University of Torino , Torino , Italy.
Expert Opin Drug Metab Toxicol. 2018 Jan;14(1):91-99. doi: 10.1080/17425255.2018.1417388. Epub 2017 Dec 19.
multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclonal antibodies, and histone deacetylase inhibitors. Areas covered: ixazomib is the first oral PI recently approved by Food and Drug Administration (FDA) and European Medicine Agency (EMA) in combination with lenalidomide and dexamethasone as salvage therapy in MM patients. In this paper, we focus on its pharmacokinetics features, as well as its safety and efficacy in clinical studies. Expert opinion: ixazomib can be considered an oral analogue of bortezomib, with 9.5-day half-life, 58% of oral bioavailability, and a large distribution volume of 543L. These features make it a versatile molecule, potentially useful both in combination and as single agent. Oral route of administration and good efficacy/safety profile are its winning characteristics, providing the rationale for a future role also in the maintenance setting.
多发性骨髓瘤(MM)是一种浆细胞疾病,是第二常见的血液系统癌症。尽管MM仍然是一种无法治愈的疾病,但在过去几十年中,由于蛋白酶体抑制剂(PIs)、免疫调节药物、单克隆抗体和组蛋白去乙酰化酶抑制剂等新型药物的引入,预后有所改善。涵盖领域:伊沙佐米是最近被美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)批准的首个口服PI,与来那度胺和地塞米松联合用于MM患者的挽救治疗。在本文中,我们重点关注其药代动力学特征,以及在临床研究中的安全性和有效性。专家观点:伊沙佐米可被视为硼替佐米的口服类似物,半衰期为9.5天,口服生物利用度为58%,分布容积大,为543L。这些特性使其成为一种通用分子,可能在联合用药和单药治疗中都有用。口服给药途径和良好的疗效/安全性是其优势,为其在维持治疗中的未来作用提供了理论依据。