Bedikian Agop Y, Vardeleon Anna, Smith Teresa, Campbell Susan, Namdari Rostam
Department of Melanoma Medical Oncology, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 430, Houston, TX 77030, USA.
J Clin Pharmacol. 2006 Jul;46(7):727-37. doi: 10.1177/0091270006288953.
Vincristine sulfate liposomes injection (VSLI) is a liposomal formulation of vincristine encapsulated in sphingosomes composed of sphinogomyelin and cholesterol (58/42; mol/mol). The pharmacokinetics and urinary excretion of VSLI were evaluated in 12 patients with metastatic melanoma after single-dose (2.0 mg/m2 every 2 weeks = 1 cycle) and multiple-dose (cycle 3, pharmacokinetics only) administrations (intravenous infusion over 1 hour). After VSLI infusion, total (released and encapsulated) vincristine concentrations in plasma remained relatively constant for 3 to 12 hours and thereafter declined, with interpatient variability seen in the rate of decline resulting in monoexponential or biexponential profiles. The area under the plasma concentration-time curve from time zero to infinity of total vincristine in plasma ranged from 4933 to 40495 h.ng/mL and total clearance ranged from 131 to 445 mL/h. The volume of distribution at steady state was 2650 +/- 731 mL, indicating VSLI was mainly confined within the plasma. The released vincristine concentrations in plasma were below the level of quantitation in 95% of samples. The pharmacokinetic parameters were similar between cycles 1 and 3, and trough plasma levels of total vincristine were below the level of quantitation of 1 ng/mL. Approximately 8% of the injected dose was excreted in the urine as unchanged vincristine (7%) or N-desformylvincristine (0.8%). Overall, VSLI exhibited a longer circulation half-life and higher area under the plasma concentration-time curve compared to conventional vincristine, whereas its route of elimination remained unchanged.
硫酸长春新碱脂质体注射液（VSLI）是一种将长春新碱包裹于由鞘磷脂和胆固醇（58/42；摩尔/摩尔）组成的鞘脂体中的脂质体制剂。对12例转移性黑色素瘤患者进行单剂量（每2周2.0mg/m² = 1个周期）和多剂量（仅第3周期进行药代动力学研究）给药（静脉输注1小时）后，评估了VSLI的药代动力学和尿排泄情况。输注VSLI后，血浆中总（释放和包裹的）长春新碱浓度在3至12小时内保持相对恒定，此后下降，患者间下降速率存在差异，导致出现单指数或双指数曲线。血浆中总长春新碱从时间零至无穷大的血浆浓度 - 时间曲线下面积范围为4933至40495 h.ng/mL，总清除率范围为131至445 mL/h。稳态分布容积为2650±731 mL，表明VSLI主要局限于血浆内。95%的样本中血浆中释放的长春新碱浓度低于定量水平。第1周期和第3周期的药代动力学参数相似，总长春新碱的谷浓度低于1 ng/mL的定量水平。约8%的注射剂量以未改变的长春新碱（7%）或N - 去甲酰长春新碱（0.8%）形式经尿液排泄。总体而言，与传统长春新碱相比，VSLI表现出更长的循环半衰期和更高的血浆浓度 - 时间曲线下面积，但其消除途径保持不变。
