Pharmacodynamic aspects of intravenous diltiazem administration

The diltiazem serum concentration and the magnitude and time course of systemic and coronary hemodynamic and ECG responses to intravenous diltiazem (250 micrograms/kg intravenous bolus plus 1.4 micrograms/kg/min infusion) were investigated in 14 patients with chronic stable angina pectoris. After 3, 8, and 15 minutes this dosing schedule produced serum concentrations of 570 +/- 259, 199 +/- 62, and 136 +/- 30 ng/ml, respectively (mean +/- SD). These drug levels were associated with a small, transient increase in heart rate (6 bpm, mean) at 3 minutes, which occurred during the nadir of the blood pressure response. But at 8 and 15 minutes, heart rate was unchanged compared to control rates, although blood pressure remained decreased (19%, p less than 0.01 at 15 minutes). Pressure-rate product was significantly reduced as left ventricular end-diastolic pressure and dP/dT remained unchanged. Systemic resistance decreased 17% (p less than 0.05) and stroke index increased 10% (p less than 0.01). Coronary flow was maintained as coronary resistance declined (14%, p less than 0.01). PR interval prolongation (14%, p less than 0.01) occurred at 15 minutes. Correlations between changes in systolic, diastolic, and mean pressures and drug concentration were significant (r = -0.59, -0.80, and -0.78, respectively, all p less than 0.05). The intercept for each regression line was approximately 96 ng/ml diltiazem concentration, suggesting that this represents the minimum effective diltiazem serum concentration. These results indicate that intravenous diltiazem is well tolerated and promptly reduces blood pressure and both systemic and coronary resistances without oxygen-wasting effects of an increase in heart rate.