ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Translational Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1631341
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
Provisionally accepted
Yingying Fang
Lu QiYu WangChunyu HanQian ZhangXiaoyun LiuJu LiuXiaoqiang ChengYinjuan LiYan LiMingli SunLong LiuPu LiYingjuan ZhangHuijuan Liu
Xinghe Wang*- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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This Phase I study aimed to evaluate the pharmacokinetics 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 if 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 Cmax, AUC0-t, and AUC0-∞ were 108.08%, 108.20%, and 110.85%, respectively. The primary metabolites of NLS (1, 2-GDN), and the GMRs of Cmax, AUC0-t, AUC0-∞ were 107.68%, 102.28% and 102.23%, respectively. Similarly, for another metabolite of NLS (1, 3-GDN), the GMRs of Cmax, AUC0-t, and AUC0-∞ were 106.56%, 102.05% and 104.67%, respectively. All 90% confidence intervals (CIs) for the test/reference AUC ratio and Cmax 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.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 the US-approved originator Nitrolingual. Clinical trial registration: http://www.chinadrugtrials.org.cn/index.html,identifier CTR20230675.
Keywords: Bioequivalence, Nitroglycerin Lingual Spray, pharmacokinetics, Safety, Early clinical trial
Received: 19 May 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Fang, Qi, Wang, Han, Zhang, Liu, Liu, Cheng, Li, Li, Sun, Liu, Li, Zhang, Liu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xinghe Wang, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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