Nitrate therapy: is there an optimal substance and formulation?

Nitrate therapy has been shown to be beneficial for the treatment of coronary artery diseases and a number of chemical entities and their respective pharmaceutical formulations are available for clinical use. In this report, the performance of these nitrate drug/formulation combinations is discussed in terms of the relative onset of action, duration of action, tolerance properties/regeneration of reactivity and patient acceptance. A pharmacodynamic action scheme is presented and this allows a systematic assessment of how changes in the nitrate and/or formulation may impact on therapeutic activity. Data suggest that several sustained-release preparations of various nitrates can provide protection against exercise-induced angina for about 12 h on repeated dosing, provided a 'nitrate-free' or 'nitrate-poor' interval is also instituted. The 'ideal' nitrate substance and formulation, which theoretically can provide around-the-clock protection, is not yet available.