脂质体包裹紫杉醇易用药（LEP-ETU）制剂与聚氧乙烯蓖麻油中紫杉醇的生物等效性：晚期癌症患者随机、双周期交叉研究。
Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) formulation and paclitaxel in polyethoxylated castor oil: a randomized, two-period crossover study in patients with advanced cancer.
机构信息
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
出版信息
Clin Ther. 2013 Dec;35(12):1946-54. doi: 10.1016/j.clinthera.2013.10.009. Epub 2013 Nov 28.
BACKGROUND
Preclinical studies comparing paclitaxel formulated with polyethoxylated castor oil with the sonicated formulation of liposome-entrapped paclitaxel (LEP) have demonstrated that LEP was associated with reduced toxicity while maintaining similar efficacy. Preliminary studies on the pharmacokinetics in patients support earlier preclinical data, which suggested that the LEP Easy-to-Use (LEP-ETU) formulation and paclitaxel formulated with castor oil may have comparable pharmacokinetic properties.
OBJECTIVES
Our objectives were: (1) to determine bioequivalence of paclitaxel pharmaceutically formulated as LEP-ETU (test) and paclitaxel formulated with castor oil (reference); and (2) to assess the tolerability of LEP-ETU following intravenous administration.
METHODS
Patients with advanced cancer were studied in a randomized, 2-period crossover bioequivalence study. Patients received paclitaxel 175 mg/m(2) administered as an intravenous infusion over 180 minutes, either as a single-treatment cycle of the test formulation followed by a single-treatment cycle of the reference formulation, or vice versa.
RESULTS
Thirty-two of 58 patients were evaluable and were included in the analysis for bioequivalence. Mean total paclitaxel Cmax values for the test and reference formulations were 4955.0 and 5108.8 ng/mL, respectively. Corresponding AUC0-∞ values were 15,853.8 and 18,550.8 ng·h/mL, respectively. Treatment ratios of the geometric means were 97% (90% CI, 91%-103%) for Cmax and 84% (90% CI, 80%-90%) for AUC0-∞. These results met the required 80% to 125% bioequivalence criteria. The most frequently reported adverse events after LEP-ETU administration were fatigue, alopecia, and myalgia.
CONCLUSION
At the studied dose regimen, LEP-ETU showed bioequivalence with paclitaxel formulated with polyethoxylated castor oil.
背景
比较紫杉醇聚氧乙烯蓖麻油制剂与包载紫杉醇的超声处理脂质体（LEP）的临床前研究表明，LEP 与毒性降低相关，同时保持类似的疗效。患者药代动力学的初步研究支持早期的临床前数据，提示 LEP 易用型（LEP-ETU）制剂和聚氧乙烯蓖麻油制剂的紫杉醇可能具有相似的药代动力学特性。
目的
我们的目的是：（1）确定 LEP-ETU 制剂（试验）和聚氧乙烯蓖麻油制剂的紫杉醇的生物等效性；（2）评估 LEP-ETU 静脉给药后的耐受性。
方法
在一项随机、2 期交叉生物等效性研究中，对晚期癌症患者进行了研究。患者接受 175 mg/m2 的紫杉醇静脉滴注，滴注时间为 180 分钟，或者是单一治疗周期的试验制剂后再进行单一治疗周期的参比制剂，或者相反。
结果
58 例患者中有 32 例可评估，纳入生物等效性分析。试验制剂和参比制剂的平均总紫杉醇 Cmax 值分别为 4955.0 和 5108.8 ng/mL。相应的 AUC0-∞值分别为 15853.8 和 18550.8 ng·h/mL。Cmax 和 AUC0-∞ 的几何均数比值的治疗比值分别为 97%（90%CI，91%-103%）和 84%（90%CI，80%-90%）。这些结果符合 80%-125%的生物等效性要求。LEP-ETU 给药后最常报告的不良事件是疲劳、脱发和肌痛。
结论
在研究的剂量方案下，LEP-ETU 与聚氧乙烯蓖麻油制剂的紫杉醇表现出生物等效性。
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