Pharmacokinetics and Pharmacodynamics of Vincristine Sulfate Liposome Injection (VSLI) in Adults With Acute Lymphoblastic Leukemia
Pharmacokinetics and Pharmacodynamics of Vincristine Sulfate Liposome Injection (VSLI) in Adults With Acute Lymphoblastic Leukemia
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DOI：
10.1002/jcph.155
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发表时间：
2013-11-01
影响因子：
2.9
通讯作者：
Deitcher, Steven R.
中科院分区：
文献类型：
--
作者：
Silverman, Jeffrey A.;Reynolds, Laurie;Deitcher, Steven R.
硫酸长春新碱脂质体注射液（VSLI）是硫酸长春新碱（VCR）的鞘磷脂和胆固醇纳米粒制剂，旨在克服标准VCR的剂量和药代动力学限制。与非脂质体VCR的快速CL和广泛组织分布相反，VSLI在血浆中循环的时间较长，CL缓慢（345 mL/h），V-d相对较小（3，570 mL）。这有助于增强和延长VCR的肿瘤组织递送。VSLI的最大耐受剂量为2.25 mg/m（2），每周一次，无剂量上限，使得非脂质体VCR在其标示剂量1.4 mg/m（2）下无法达到的个体和累积VCR暴露量。VSLI与剂量依赖性外周神经毒性相关，尽管剂量是标准VCR的2 - 3倍。VCR剂量强化联合VSLI与复发性和/或难治性急性淋巴细胞白血病成人患者的总体缓解概率增加和完全缓解增加的强烈趋势相关。总体而言，VSLI通过促进增加剂量强化，同时保持可预测和可管理的安全性特征，改善了治疗指数。
Vincristine sulfate liposome injection (VSLI,) is a sphingomyelin and cholesterol nanoparticle formulation of vincristine sulfate (VCR) that was designed to overcome the dosing and pharmacokinetic limitations of standard VCR. In contrast to the rapid CL and wide tissue distribution of non-liposomal VCR, VSLI circulates in plasma for a prolonged period of time, with a slow CL of 345mL/h and relatively small V-d of 3,570mL. This facilitates enhanced and prolonged tumor-tissue delivery of VCR. The maximum tolerated dose of VSLI, 2.25mg/m(2) once per week without a dose cap, enables individual and cumulative VCR exposure unachievable with non-liposomal VCR at its labeled dose of 1.4mg/m(2). VSLI is associated with a dose-dependent peripheral neurotoxicity albeit at doses that are two to three times that of standard VCR. VCR dose intensification with VSLI correlated with an increased probability of overall response and a strong trend towards increased complete response in adults with relapsed and/or refractory acute lymphoblastic leukemia. Overall, VSLI improves the therapeutic index by facilitating increased dose intensification while maintaining a predictable and manageable safety profile.