[Bioavailability of sustained-release and nonsustained-release isosorbide-5-mononitrate]

Bioavailability of Sustained Release and Non Sustained Release Isosorbide-5-Mononitrate. In a randomized, open cross-over study in 18 healthy subjects plasma concentration of isosorbide-5-mononitrate (IS-5-MN) after oral administration was determined over 24 h by gas chromatography. A single dose of three sustained release and two standard preparations was given: (A) a capsule (Elantan), 50 mg; (B) a development tablet, 50 mg and (C) a development capsule, 100 mg; furthermore (D) and (E) non sustained release tablets, 40 and 2 x 20 mg, of two different producers. (D) was considered as reference preparation. Standard preparations (D) and (E) were bioequivalent. But maximum plasma concentrations (cmax) of all sustained release preparations were significantly lower from 13% (C) to 53% (A). Also the moment of maximum plasma concentrations (tmax) occurred significantly later between 2 h 40 min and 3 h 50 min. A significant loss in relative bioavailability was observed for (A) with 82.5% and for (C) with 81.4%. (B) achieved the highest relative bioavailability (93.9%) of the sustained release preparations (n.s.). "Therapeutic concentrations" above 100 ng/ml over 24 h were maintained only by (C). Terminal elimination half-lives were calculated between 5.5 and 6.5 h (mean). Plasma concentration-time curves were simulated in steady state.