Wu Guolan, Wu Lihua, Zhou Huili, Lin Meihua, Peng Ling, Wang Yina, Zhai You, Hu Xingjiang, Zheng Yunliang, Lv Duo, Liu Jian, Shentu Jianzhong
Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Front Pharmacol. 2019 Jul 11;10:774. doi: 10.3389/fphar.2019.00774. eCollection 2019.
The aim of this study was to compare the pharmacokinetics and safety between two vinorelbine formulations [a new oil-in-water emulsion formulation (ANX) versus a previously marketed solution formulation (Navelbine)] in Chinese patients with advanced non-small cell lung cancer (NSCLC). This was a single-center, randomized, open-label study. Eligible patients aged 18-70 years who had histologically or cytologically confirmed NSCLC were enrolled. In cycle 1, the patients alternatively received the two formulations (30 mg/m, given as a 10-min infusion) with a 7-day interval. Samples for pharmacokinetic analysis were taken during cycle 1. For all subsequent 21-day cycles (maximum four cycles), ANX was administered on days 1 and day 8. Bioequivalence analysis was performed on C, AUC, and AUC. The safety profiles and anti-tumor effects were also determined. From March 2013 to January 2015, 24 patients were enrolled and 20 were eligible for pharmacokinetic evaluation. The 20 subjects in the pharmacokinetic analysis set had a median age of 61 years (range, 37-70 years), and 15 patients were male (75%). Mean vinorelbine C values for ANX and Navelbine were 1,317.40 and 1,446.30 ng/mL, respectively. Corresponding AUC values were 797.08 and 924.26 ng·h/mL, respectively. AUC values were 830.14 and 957.16 ng·h/mL, respectively. Treatment ratios of the geometric means were 90.00% (90% CI, 83.22-99.07%) for C, 86.92% (90% CI, 80.91-93.37%) for AUC, and 87.44% (90% CI, 82.08-93.16%) for AUC. These results met the required 80-125% bioequivalence criteria. The most frequently reported adverse events after vinorelbine administration were neutropenia, leucopenia, neutropenic fever, and constipation. At therapeutic dosage levels, pharmacokinetic behavior and safety profiles were similar for both formulations. Chinese National Registry Code: ChiCTR-IPR-15005856.
本研究旨在比较两种长春瑞滨制剂（一种新的水包油乳剂制剂（ANX）与先前上市的溶液制剂（诺维本））在中国晚期非小细胞肺癌（NSCLC）患者中的药代动力学和安全性。这是一项单中心、随机、开放标签研究。纳入年龄在18至70岁之间、经组织学或细胞学确诊为NSCLC的合格患者。在第1周期，患者交替接受两种制剂（30mg/m²，静脉滴注10分钟），间隔7天。在第1周期采集药代动力学分析样本。在随后所有的21天周期（最多4个周期）中，于第1天和第8天给予ANX。对Cmax、AUC和AUC进行生物等效性分析。还确定了安全性概况和抗肿瘤效果。2013年3月至2015年1月，共纳入24例患者，其中20例符合药代动力学评估条件。药代动力学分析集中的20名受试者中位年龄为61岁（范围37至70岁），15例为男性（75%）。ANX和诺维本的长春瑞滨平均Cmax值分别为1317.40和1446.30ng/mL。相应的AUC值分别为797.08和924.26ng·h/mL。AUC值分别为830.14和957.16ng·h/mL。几何均值的治疗比率Cmax为90.00%（90%CI，83.22 - 99.07%），AUC为86.92%（90%CI，80.91 - 93.37%），AUC为87.44%（90%CI，82.08 - 93.16%）。这些结果符合80 - 125%的生物等效性标准要求。长春瑞滨给药后最常报告的不良事件为中性粒细胞减少、白细胞减少、中性粒细胞发热和便秘。在治疗剂量水平下，两种制剂的药代动力学行为和安全性概况相似。中国国家注册代码：ChiCTR - IPR - 15005856。
