Comparison of the initial hemodynamic effects of immediate-release versus sustained-release isosorbide-5-mononitrate following single oral doses

In this double-blind, randomized, placebo-controlled cross-over study the a uthors investigated the initial time course of effects of isosorbide-5-mono nitrate (IS-5-MN) on hemodynamic parameters in 15 healthy male volunteers a fter administering a single oral dose of either an immediate-release formul ation (IS-5-MN 20 mg) or of a sustained-release formulation (IS-5-MN 50 mg) . The latter formulation released 15 mg IS-5-MN immediately, while 35 mg of the dose was sustained release. The onset of effect on the a/b-ratio of th e finger pulse curve (20 minutes after administration) and on heart rate fo llowing orthostatic challenge (30 minutes) was not different following inge stion of either the immediate-release or the sustained-release formulation. Only the systolic blood pressure following orthostatic challenge was affec ted earlier after ingestion of the immediate-release form of IS-5-MN(10 vs. 30 minutes). There was no statistically significant difference in the maxi mum effect on the measured hemodynamic parameters between the two formulati ons. There was no significant difference with respect to the effect per dos e between both of the active treatments (i.e., IS-5-MN 20 mg immediate rele ase and IS-5-MN 50 mg sustained release) within 6 hours after administratio n. The hemodynamic findings were consistent with the observed rates of the increase of plasma concentrations of IS-5-MN following both formulations. T hus, the administration of the sustained-release formulation of IS-5-MN 50 mg caused similar maximum effects when compared with an immediate-release f ormulation (20 mg). While the onset of effect of IS-5-MN on the a/b-ratio o f the finger pulse curve and on heart rate following orthostasis was simila r after administration of either the immediate- or the sustained-release fo rmulation, the onset of effect of the sustained-release formulation on syst olic blood pressure orthostasis was determined slightly later. However, the latter difference seems to be of minor clinical relevance. Journal of Clin ical Pharmacology, 2000;40:168-176 (C)2000 the American College of Clinical Pharmacology.