Drug Design, Development and Therapy (Jul 2025)
Pharmacokinetics and Safety with Bioequivalence of Isosorbide Mononitrate Sustained-Release Tablets in Chinese Healthy Volunteers: Bioequivalence Study
Abstract
Binbin Wu,1 Wei Wang,2 Qikun Zhang,3 Guigui Yu,1 Jingjing Lin,1 Ting Zhang,1 Luxi Ye,1 Keli Wang,4 Wanggang Zhang,5,* Xinyi Wu5,* 1Department of Nephrology, Zhejiang Hospital, Hangzhou, 310030, People’s Republic of China; 2Department of Emergency, Pingyang Hospital of Wenzhou Medical University, Wenzhou, 325400, People’s Republic of China; 3School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, 310053, People’s Republic of China; 4Nanjing Jiening Pharmaceutical Technology Co., Ltd, Nanjing, 211112, People’s Republic of China; 5Phase I Clinical Trial Center, Zhejiang Hospital, Hangzhou, 310030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinyi Wu, Phase I Clinical Trial Center, Zhejiang Hospital, Hangzhou, 310030, People’s Republic of China, Tel +86 17816323360, Email [email protected]: Isosorbide mononitrate was recommended for controlling anginal symptoms in patients with cardiovascular disease. We aimed to compare the pharmacokinetics, bioequivalence and safety of two formulations of oral isosorbide mononitrate sustained-release tablets in healthy Chinese volunteers.Subjects and Methods: A randomized, open-label, two-period, single-center, single-dose clinical trial with crossover design was conducted in Zhejiang Hospital. Subjects received single dose 40-mg/tablet isosorbide mononitrate in each period with a 5-day washout. Serial blood samples were collected over 36 hours post-dose (Days 1 and 6). The plasma concentrations of isosorbide mononitrate were measured using a high-performance liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters were determined using noncompartmental methods.Results: Fifty-six healthy subjects were enrolled. In the fasting group, the maximum plasma concentration (Cmax, mean ± SD) was 487.54 ± 69.17 ng/mL at 3.75 (1.50, 6.00) hours (median [min, max]) for test formulation, and 529.76 ± 84.64 ng/mL at 4.00 (2.50, 5.50) hours for reference formulation. In the fed group, Cmax was 501.46 ± 68.80 ng/mL at 4.50 (1.50, 6.50) hours for test formulation, and 535.14 ± 69.89 ng/mL at 4.00 (1.50, 9.00) hours for reference formulation. All 90% confidence intervals for Cmax, AUC0-t and AUC0-∞ fell within the 80– 125% bioequivalence range under both fasting and fed conditions. No drug-related serious adverse events were observed throughout the trial.Conclusion: The isosorbide mononitrate sustained-release tablet demonstrated bioequivalence to the reference formulation (Ismo® retard) under both fasting and fed conditions, with comparable safety profiles. Both formulations were well tolerated.Keywords: isosorbide mononitrate, bioequivalence, pharmacokinetics, safety, Chinese healthy volunteers
