Coronary vasodilation with dihydropyridines--a pharmacokinetic study

In 26 patients with coronary artery disease, the mean diameters of angiographically 'normal' epicardial coronary arteries were assessed with the aid of a computer-assisted contour detection system (CAAS) before and up to 15 min after onset of a 4-min intravenous-infusion of 2 mg nifedipine (13 patients, group I) or 1 mg nisoldipine (13 patients, group II). Maximal coronary dilation amounted to 20 +/- 9% (4th min) in group I and to 18 +/- 9% (15th min) in group II. In addition, in group II changes of the minimal diameters of 9 coronary obstructions were measured; the maximum increase averaged 28 +/- 15% (7th min). In order to compare the pharmacokinetic properties of these compounds the dilation of the 'normal' coronary segments was correlated with the respective drug plasma levels; maximal plasma concentrations averaged 62 +/- 21 ng ml-1 (7th min) in group I and 17 +/- 7 ng ml-1 (4th min) in group II respectively. A positive, linear correlation between coronary dilation and plasma levels was only found with nifedipine (P less than 0.05); with nisoldipine, however, coronary dilation developed in form of a hysteresis curve, when plotted against plasma levels, probably due to the high receptor affinity of this substance. The prolonged efficacy of nisoldipine could be favourable in oral long-term treatment of patients with coronary artery disease.