College of Pharmacy, Yeungnam University, Gyeongsan, Kyungbuk, Korea.
Ann Pharmacother. 2010 Jan;44(1):117-26. doi: 10.1345/aph.1M380. Epub 2009 Dec 15.
To evaluate the literature characterizing the mechanism of action, pharmacokinetics, pharmacodynamics, and therapeutic efficacy of plerixafor for hematopoietic stem cell (HSC) mobilization for autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma.
A PubMed search (1966-September 2009) was conducted using the key words plerixafor and AMD3100. Manufacturer's prescribing information was also used.
English-language articles were selected and data were extracted with a focus on clinical studies of HSC mobilization in patients with NHL or multiple myeloma.
Plerixafor exerts its effect by reversibly blocking the ability of HSC to bind to the bone marrow matrix. When used with granulocyte colony-stimulating factor (G-CSF), plerixafor helps increase the number of HSCs in the peripheral blood, where they can be collected for use in autologous transplantation. In clinical studies, plerixafor was rapidly absorbed after subcutaneous injection, reaching a maximum plasma concentration at approximately 0.5 hours. Plerixafor is renally excreted as the parent drug, with an elimination half-life ranging from 3 to 5 hours. Plerixafor increases circulating CD34+ cells in the peripheral blood, with a peak effect about 6-9 hours after subcutaneous administration. An approximate 2- to 3-fold increase in the CD34+ cell count is seen by the first dose of plerixafor after 4 consecutive days of G-CSF treatment. In 2 Phase 3 studies in patients with NHL or multiple myeloma, addition of plerixafor to G-CSF resulted in a higher CD34+ cell collection with fewer apheresis days, but failed to show better graft durability or overall patient survival for up to 12 months of follow-up.
Clinical trials have demonstrated that the addition of plerixafor to G-CSF was beneficial for HSC mobilization to peripheral blood for collection and subsequent transplantation in patients with NHL or multiple myeloma. Further studies should assess the benefit of the additive use of plerixafor on clinical outcomes.
评估培瑞克昔福促进造血干细胞（HSC）动员用于非霍奇金淋巴瘤（NHL）或多发性骨髓瘤患者自体移植的作用机制、药代动力学、药效学和治疗效果的文献。
使用关键词培瑞克昔福和 AMD3100 在 PubMed 上进行了 1966 年-2009 年 9 月的检索。还使用了制造商的处方信息。
选择了英文文章，并重点提取了 NHL 或多发性骨髓瘤患者 HSC 动员的临床研究数据。
培瑞克昔福通过可逆地阻断 HSC 与骨髓基质结合的能力发挥作用。当与粒细胞集落刺激因子（G-CSF）一起使用时，培瑞克昔福有助于增加外周血中的 HSC 数量，以便在自体移植中使用。在临床研究中，培瑞克昔福皮下注射后迅速吸收，约 0.5 小时达到最大血浆浓度。培瑞克昔福作为母体药物经肾脏排泄，消除半衰期为 3 至 5 小时。培瑞克昔福增加外周血循环中的 CD34+细胞，皮下给药后约 6-9 小时达到峰值效应。在 NHL 或多发性骨髓瘤患者的 2 项 3 期研究中，在 G-CSF 治疗的第 4 天连续给予培瑞克昔福第 1 剂后，CD34+细胞计数增加约 2-3 倍。在 NHL 或多发性骨髓瘤患者中，培瑞克昔福联合 G-CSF 可提高 CD34+细胞采集量，减少单采天数，但未能显示在长达 12 个月的随访中更好的移植物耐久性或患者总体生存率。
临床试验表明，培瑞克昔福联合 G-CSF 有利于 NHL 或多发性骨髓瘤患者外周血中 HSC 的动员采集，随后进行移植。应进一步研究评估培瑞克昔福的附加使用对临床结果的益处。
