Wu Binbin, Wang Wei, Zhang Qikun, Yu Guigui, Lin Jingjing, Zhang Ting, Ye Luxi, Wang Keli, Zhang Wanggang, Wu Xinyi
Department of Nephrology, Zhejiang Hospital, Hangzhou, 310030, People's Republic of China.
Department of Emergency, Pingyang Hospital of Wenzhou Medical University, Wenzhou, 325400, People's Republic of China.
Drug Des Devel Ther. 2025 Jul 14;19:6025-6035. doi: 10.2147/DDDT.S508202. eCollection 2025.
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.
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.
Fifty-six healthy subjects were enrolled. In the fasting group, the maximum plasma concentration (C, 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, C 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 C, AUC and AUC fell within the 80-125% bioequivalence range under both fasting and fed conditions. No drug-related serious adverse events were observed throughout the trial.
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.
单硝酸异山梨酯被推荐用于控制心血管疾病患者的心绞痛症状。我们旨在比较两种口服单硝酸异山梨酯缓释片在中国健康志愿者中的药代动力学、生物等效性和安全性。
在浙江医院进行了一项随机、开放标签、两周期、单中心、单剂量的交叉设计临床试验。受试者在每个周期接受单剂量40mg/片的单硝酸异山梨酯，洗脱期为5天。给药后36小时（第1天和第6天）采集系列血样。采用高效液相色谱-串联质谱法测定单硝酸异山梨酯的血浆浓度，并用非房室方法确定药代动力学参数。
招募了56名健康受试者。在空腹组中，试验制剂在3.75（1.50，6.00）小时（中位数[最小值，最大值]）时的最大血浆浓度（C，平均值±标准差）为487.54±69.17ng/mL，参比制剂在4.00（2.50，5.50）小时时为529.76±84.64ng/mL。在进食组中，试验制剂在4.50（1.50，6.50）小时时的C为501.46±68.80ng/mL，参比制剂在4.00（1.50，9.00）小时时为535.14±69.89ng/mL。在空腹和进食条件下，C、AUC和AUC的所有90%置信区间均落在80%-125%的生物等效性范围内。在整个试验过程中未观察到与药物相关的严重不良事件。
单硝酸异山梨酯缓释片在空腹和进食条件下均显示出与参比制剂（依姆多缓释片）的生物等效性，安全性相当。两种制剂耐受性均良好。
