Relative bioavailability of two isosorbide dinitrate sublingual tablet formulations administered as single doses in healthy subjects
Niopas, I.; Daftsios, A.C.; Nikolaidis, N.
International Journal of Clinical Pharmacology and Therapeutics 39(5): 224-228
2001
ISSN/ISBN: 0946-1965 PMID: 11380069 Accession: 011278120
Objective: The purpose of this study was to evaluate the relative bioavailability and bioequivalence of a test and a reference sublingual tablet each containing 5 mg of isosorbide dinitrate in healthy volunteers. Methods: The study was conducted as an open-label, randomized, single-dose, two-period crossover design in 20 healthy volunteers with a washout period of 7 days, under fasting conditions. Plasma concentrations of the major active metabolite isosorbide 5-mononitrate were quantified, using a validated capillary gas chromatographic assay, with electron-capture detection. The pharmacokinetic parameters used to assess the bioequivalence of the two preparations were AUC0-infin and AUC0-t for the extent of absorption and Cmax and tmax for the rate of absorption. Results: The calculated 90% confidence intervals of the geometric mean values of the test/reference ratios were 98.2% to 103.2% (point estimate; 100.7%) for AUC0-infin, 96.9% to 103.8% (point estimate; 100.3%) for AUC0-t, and 87.9% to 98.2% (point estimate; 92.9%) for Cmax. No statistically significant difference was found for tmax and elimination half-life (t1/2) values. Conclusion: From the results of the present study, it is concluded that the test and reference isosorbide dinitrate sublingual preparations are bioequivalent in both extent and rate of absorption and it can be assumed that they are therapeutically equivalent and exchangeable in clinical practice.