Pharmacokinetics and Safety with Bioequivalence of Isosorbide Mononitrate Sustained-Release Tablets in Chinese Healthy Volunteers: Bioequivalence Study.

PURPOSE

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 (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.

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.