Nitrate therapy without loss of action by correct dosage.

Previous studies carried out with ISDN prove that long lasting, unfluctuating plasma concentrations--e.g. above 300 ng IS-5-N/ml--cause a severe loss of action. This could be cancelled by administration of isosorbide dinitrate (ISDN) according to a regimen in which an interval with considerably reduced nitrate levels is guaranteed. On the other hand a dosage regimen which leads to steady state plasma concentrations which fluctuate between 100 and 300 ng IS-5-N/ml (after 3 times daily 20 mg ISDN) showed no clinically significant loss of efficacy even after 4 weeks of application. Based on these findings a therapy like once daily 120 mg ISDN sustained release which guarantees plasma levels of up to 600 ng IS-5-N/ml (over the active day of the patient) with an interval of nitrate levels down to 100 ng (overnight) could be judged as efficient. As recent studies showed there is no clinically found loss of efficacy after four week application. With regard to a better compliance this regimen seemed to be the optimum.