The haemodynamic and anti-ischaemic effects of a single tablet of 80 mg isosorbide dinitrate in slow-release formulation and a review of nitrate tolerance.

There is increasing evidence that relatively constant plasma nitrate concentrations induced by 3-times-daily administration of isosorbide dinitrate can lead to an attenuation or even complete loss of the drug's anti-ischaemic effects (nitrate tolerance). We therefore assessed the dependence of nitrate tolerance development from the haemodynamic and anti-ischaemic effects of a slow-release tablet formulation of isosorbide dinitrate 80 mg, administered according to different daily dosage regimens in patients with angina. It was found that a once-daily regimen, with its consequent peak and trough plasma nitrate concentrations, is capable of protecting against exercise-induced myocardial ischaemia for about 12 hours with the circumvention of nitrate tolerance.