Relative bioavailability of two isosorbide dinitrate sublingual tablet formulations administered as single doses in healthy subjects.
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 AUC(0-infinity) and AUC(0-infinity) 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 AUC(0-infinity) 96.9% to 103.8% (point estimate; 100.3%) for AUC(0-infinity), and 87.9% to 98.2% (point estimate; 92.9%) for Cmax. No statistically significant difference was found for tmax and elimination half-life (t 1/2) values.


CONCLUSIONS
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.
Niopas
I
I
Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, Greece. niopas@pharm.auth.gr
Daftsios
A C
AC
Nikolaidis
N
N
D000286:Administration, Sublingual; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D013810:Therapeutic Equivalency; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate