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European Heart Journal 1989 10(Supplement F):137-141; doi:10.1093/eurheartj/10.suppl_F.137
Copyright © 1989 by the European Society of Cardiology.
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© 1989 The European Society of Cardiology

Drug plasma levels and coronary vasodilation after isosorbide dinitrate chewing capsules

S. Jost, W. Rafflenbeul, I. Knop, C. Bossaller, D. Gulba, H. Hecker, P. Lippolt and P. R. Lichtlen

Hannover Medical School Hannover, F.R.G.

Address for reprints: Dr Stefan Jost. Medizinische Hochschule Hannover, Abteilung Kardiologie, Postfach 61 01 80, D-3000 Hannover 61, F.R.G.

Five, ten and fifteen min after sublingual administration of 10 mg isosorbide dinitrate (ISDN) in chewing capsules, in 10 patients with coronary artery disease, ISDN plasma levels were correlated with the dilation of epicardial coronary arteries as well as with changes in aortic blood pressure and heart rate. Due to the rapid and extensive drug absorption, maximal ISDN plasma levels averaged 138±73ng ml–1 and were already obtained after 5 min; they declined to 102±76and 602±34ng ml–1 in the 10th and 15th min respectively. In 7 patients isosorbide mononitrate plasma levels were still negligibly low (<30ng ml–1). Mean diameters of ‘normal’ coronary segments increased by an average of 20±10%, 26±11% and 27±13% (P<0·001) at 5, 10 and 15 min respectively compared to control. The maximal drop in systolic aortic pressure (147±19 to 115±15 mmHg; P<0·01) as well as the maximal increase in heart rate (66±4 to 80±11 beats min–1; P<0·01) were observed in the 15th min; diastolic aortic pressure and double product remained constant. Due to the long persistence of coronary dilation andhaemodynamic changes, none of these drug effects correlated significantly with the ISDN plasma levels.

In addition, the minimal diameters of 10 coronary stenoses were measured in 7 patients; with ISDN 7 stenoses showed dilation ranging from 23% to 98%.

ISDN chewing capsules can be suitable for the immediate relief of anginal attacks as well as for rapid, potent and prolonged coronary dilation during coronary angiography.

Key Words: Isosorbide dinitrate chewing capsules • coronary vasodilation • pharmacokinetics • isosorbide dinitrate plasma levels


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