Bioequivalence study of voriconazole for intravenous infusion in healthy Chinese subjects under fasting conditions

IF 3.7 3区医学 Q2 CHEMISTRY, MEDICINAL

Journal of pharmaceutical sciences Pub Date : 2025-02-01 DOI:10.1016/j.xphs.2024.12.012

Zhangqiang Xiang , Mupeng Li , Shaoting Cui , Chunyan Gan , Fangfang Liu , Qian Huang , Gang Mai , Lianlian Fan

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引用次数: 0

Abstract

Objective

Voriconazole, a second-generation triazole, is used to prevent and treat invasive fungal infections. This study aimed to assess the bioequivalence and safety of test and reference voriconazole intravenous infusion under the fasting conditions.

Methods

The study employed a randomized, open-label, single-dose, two-period, crossover trial design. Eligible subjects randomly assigned for screening, receiving either the test or reference voriconazole for intravenous infusion during the first period, with alternative products administered during the second period. The washout period lasted 7 days. The single administration dosage was fixed at 6 mg/kg. Nineteen blood samples were collected at pre-dose and up to 46 h post-dose for each subject. The validated LC-MS/MS method was used to determine the concentration of voriconazole in plasma.

Results

Twenty-four subjects were enrolled in the study, comprising 20 males and 4 females. The primary pharmacokinetic parameters (mean ± SD) were as follows: C_max was 4631.20 ± 744.80 and 5008.09 ± 1020.77 ng/mL, AUC_0-t was 27,121.07 ± 12,658.03 and 28,674.08 ± 13,118.05 ng*h/mL, and AUC_0-∞ was 28,056.10 ± 14,428.76 and 29,616.29 ± 14,783.70 ng*h/mL for the test and reference formulations, respectively. The 90 % confidence intervals of geometric mean ratios for C_max, AUC_0-t, and AUC_0-∞ fell within the range of 80.00 % to 125.00 %. Both products were well tolerated and no serious adverse event was observed.

Conclusion

The test and reference voriconazole intravenous infusion demonstrated bioequivalence and good tolerability.

查看原文本刊更多论文

静脉输注伏立康唑在中国健康受试者空腹条件下的生物等效性研究。

目的：Voriconazole是第二代三唑类药物，用于预防和治疗侵袭性真菌感染。本研究旨在评价试验用伏立康唑静脉输注与对照用伏立康唑在空腹条件下的生物等效性和安全性。方法：采用随机、开放标签、单剂量、两期交叉试验设计。符合条件的受试者被随机分配进行筛查，在第一阶段接受测试或参考伏立康唑静脉输注，在第二阶段使用替代产品。洗脱期为7 d。单次给药剂量固定为6mg/kg。每个受试者在给药前和给药后46小时采集了19份血液样本。采用经验证的LC-MS/MS方法测定血浆中伏立康唑的浓度。结果：共纳入受试者24人，其中男性20人，女性4人。主要药代动力学参数（mean±SD）为：Cmax为4631.20±744.80和5008.09±1020.77 ng/mL， AUC0-t分别为27121.07±12658.03和28674.08±13118.05 ng*h/mL， AUC0-∞分别为28056.10±14428.76和29616.29±14783.70 ng*h/mL。Cmax、AUC0-t和AUC0-∞的几何平均比率的90%置信区间在80.00% ~ 125.00%之间。两种产品耐受性良好，未观察到严重的不良事件。结论：伏立康唑静脉滴注具有良好的生物等效性和耐受性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of pharmaceutical sciences 医学-化学综合

CiteScore

7.30

自引率

13.20%

发文量

367

审稿时长

33 days

期刊介绍： The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.