高变异性硝酸甘油口腔喷雾剂（NLS）与美国获批的硝酸甘油口腔喷雾剂参比产品（Nitrolingual）的药代动力学和安全性：一项随机、四周期、四序列、部分重复交叉的I期生物等效性临床试验。

Pharmacokinetics and safety of highly variable nitroglycerin lingual spray (NLS) versus US-licensed nitroglycerin lingual spray reference product (Nitrolingual): a randomized, four-cycle, four-sequence, partially replicated crossover Phase I bioequivalence clinical trial.

作者信息

Fang Yingying, Qi Lu, Wang Yu, Han Chunyu, Zhang Qian, Liu Xiaoyun, Liu Ju, Cheng Xiaoqiang, Li Yinjuan, Li Yan, Sun Mingli, Liu Long, Li Pu, Zhang Yingjuan, Liu Huijuan, Wang Xinghe

机构信息

Department of Phase I Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

出版信息

Front Pharmacol. 2025 Aug 28;16:1631341. doi: 10.3389/fphar.2025.1631341. eCollection 2025.

DOI:10.3389/fphar.2025.1631341

PMID:40949117

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12422889/

Abstract

PURPOSE

In this Phase I study, we aimed to evaluate the pharmacokinetic bioequivalence and the safety of a nitroglycerin lingual spray (NLS) compared with US-approved Nitrolingual in healthy subjects.

METHODS

Subjects (N = 56) were randomized 1:1 to receive one 96-mg NLS, US-approved Nitrolingual; safety was assessed for 11 days. Bioequivalence was evaluated using the average bioequivalence method to test whether the 90% confidence intervals (CIs) of the geometric means (NLS vs. US-approved Nitrolingual) for the primary endpoints were within prespecified acceptable ranges (80%-125%).

RESULTS

After the single administration of NLS (test preparation vs. reference preparation) under fasting conditions, the geometric mean ratios (GMRs) of C, AUC, and were 108.08%, 108.20%, and 110.85%, respectively. For the primary metabolites of NLS (1, 2-GDN), the GMRs of C, AUC, were 107.68%, 102.28%, and 102.23%, respectively. Similarly, for another metabolite of NLS (1, 3-GDN), the GMRs of C, AUC, and were 106.56%, 102.05%, and 104.67%, respectively. All 90% CIs for the test/reference AUC ratio and C ratio were within the acceptable range (80%-125%) for BE, which met the requirements of bioequivalence. No serious adverse events (AEs) occurred, and all AEs were mild and transient.

CONCLUSION

The bioequivalence of NLS to US-approved Nitrolingual was demonstrated; the safety results of the two study drugs were also similar. These studies provided robust evidence of the pharmacokinetics similarity between NLS and US-approved originator Nitrolingual.

CLINICAL TRIAL REGISTRATION

http://www.chinadrugtrials.org.cn/index.html, identifier CTR20230675.

摘要

目的

在本I期研究中，我们旨在评估硝酸甘油舌喷雾剂（NLS）与美国批准的硝酸甘油舌下喷雾剂（Nitrolingual）在健康受试者中的药代动力学生物等效性和安全性。

方法

将受试者（N = 56）按1:1随机分组，分别接受一次96毫克的NLS或美国批准的Nitrolingual；对安全性进行了11天的评估。使用平均生物等效性方法评估生物等效性，以测试主要终点的几何均值（NLS与美国批准的Nitrolingual）的90%置信区间（CI）是否在预先指定的可接受范围内（80%-125%）。

结果

在禁食条件下单次给予NLS（试验制剂与参比制剂）后，C、AUC和的几何均值比（GMR）分别为108.08%、108.20%和110.85%。对于NLS的主要代谢物（1, 2-甘油二硝酸酯），C、AUC和的GMR分别为107.68%、102.28%和102.23%。同样，对于NLS的另一种代谢物（1, 3-甘油二硝酸酯），C、AUC和的GMR分别为106.56%、102.05%和104.67%。试验/参比AUC比和C比的所有90%CI均在生物等效性的可接受范围内（80%-125%），符合生物等效性要求。未发生严重不良事件（AE），所有AE均为轻度且短暂性的。