Drug plasma levels and coronary vasodilation after isosorbide dinitrate chewing capsules

Five, ten and fifteen min after sublingual administration of 10mg 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 +/- 73 ng ml-1 and were already obtained after 5 min; they declined to 102 +/- 76 and 62 +/- 34 ng ml-1 in the 10th and 15th min respectively. In 7 patients isosorbide mononitrate plasma levels were still negligibly low (less than 30 ng ml-1). Mean diameters of 'normal' coronary segments increased by an average of 20 +/- 10%, 26 +/- 11% and 27 +/- 13% (P less than 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 less than 0.01) as well as the maximal increase in heart rate (66 +/- 4 to 80 +/- 11 beats min-1; P less than 0.01) were observed in the 15th min; diastolic aortic pressure and double product remained constant. Due to the long persistence of coronary dilation and haemodynamic 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%.(ABSTRACT TRUNCATED AT 250 WORDS)