Performance of a slow-release formulation of isosorbide-5-mononitrate (ISMO retard).
From the in vitro release-rate constant of a new sustained-release (SR) preparation of 40 mg isosorbide-5-mononitrate, the concentration-time profile in healthy subjects could be excellently predicted. Therapeutically, effective concentrations of 100 ng/ml were achieved within 20 min and lasted up to a maximum of 15.6 h. The decline of concentrations below this value thereafter, guarantees the absence of tolerance development in chronic therapy. In a three-period change-over study, two other commercial SR preparations exhibited only 79% and 53% of the bioavailability of the new formulation, which was significant in both cases. Compared with literature data, the absolute bioavailability of the new form should lie in the order of at least 85%.