[Controlled clinical studies of tolerance development and dosing problems in nitrate therapy]

The phenomenon of development of tolerance to nitroglycerine as well as avoidance of this through a nitrate-free interval was known 100 years ago. Concerning the haemodynamic and anti-ischaemic effect of organic nitrates in therapy, the development of a tolerance is a clinical problem that is much discussed. Conducive to tolerance are obviously continuous application, short dosing intervals and high-dosage level so that an anti-ischaemic protection or rather, for heart insufficiency a haemodynamic relief, cannot be achieved by using organic nitrates around the clock. On the contrary, keeping a nitrate-free interval of 12 to 18 hours allows proof of the effect of at least 12 hours under IS-5-MN as is also the case under s.r. ISDN or 8 hours under nitroglycerine-patches. In this case, a lack of anti-ischaemic protection in the interval, particularly in the early morning hours, has to be accepted.