Abstract
In 1980 a placebo-controlled double-blind study was published by us demonstrating a clear development of tolerance to the antiischemic effect of isosorbide dinitrate (ISDN) in slow-release (s.r.) form during long-term treatment with 20, 40, or 60 mg three times daily [1, 11]. These results were at that time actively discussed as they showed that the widely used — but at that time not proven — administration of ISDN s.r. t.i.d. is equivalent to a placebotreatment. This study induced us to make further investigations to assess the following:
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1.
whether tolerance, independent of the galenic formulation, is an inherent property of ISDN longterm treatment;
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2.
the temporal course of development and reversal of tolerance;
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3.
whether the antiischemic and hypotensive effects of ISDN show a different response in respect to tolerance development;
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4.
the interaction between nitrate plasma concentration and tolerance development;
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5.
the clinical significance of a possible cross-tolerance to the antiischemic effect of sublingually administered nitroglycerin (GTN); and
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6.
whether tolerance can be avoided by intermittent administration.
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References
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Blasini, R., Reiniger, G., Brügmann, U. (1985). Tolerance to the Antiischemic Effect of Isosorbide Dinitrate during Continuous but not during Intermittent Oral Therapy. In: Cohn, J.N., Rittinghausen, R. (eds) Mononitrates. International Boehringer Mannheim Symposia. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-70234-1_17
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