Acute and chronic studies of diltiazem in elderly versus young hypertensive patients

The pharmacodynamics, disposition and hormonal responses to acute intravenous and chronic oral diltiazem treatment were compared in young and elderly hypertensive patients. In elderly patients, supine diastolic blood pressure decreased significantly during the first week of treatment (baseline mean ± standard error of the mean, 100 ± 1 to 93 ± 2 mm Hg) and decreased further during the study to 86 ± 2 mm Hg at the end of the study. Diastolic blood pressure of the young patients decreased significantly by the third week of treatment (from 104 ± 2 to 97 ± 3 mm Hg) and decreased further during the study to 94 ± 2 mm Hg at the end of the study. Baseline supine systolic blood pressure was greater in elderly than in young patients (167 ± 5 vs 144 ± 3 mm Hg; p <0,01) and was significantly reduced in the elderly by the fourth week (167 ± 5 to 154 ± 3 mm Hg; p <0.003), with a significant reduction sustained throughout the 14-week period. Young patients had little change in systolic blood pressure. Supine heart rate tended to decrease in both groups during the 14-week period. Acute intra-venous diltiazem pharmacokinetics determined at the beginning of the study showed that total diltiazem clearance was similar in elderly (13.3 ± 1.0 ml/min/kg) and young (13.7 ± 1.9 ml/min/kg) patients as was volume of distribution (4.2 ± 0.3 vs 4.3 ± 0.6 liters/kg) and elimination half-life (3.78 ± 0.19 vs 3.69 ± 0.23 hours). After 2 weeks of oral diltiazem treatment at a dose of 120 mg twice daily, elimination half-life was prolonged in both elderly (3.78 ± 0.19 to 5.80 ± 0.48 hours; p <0.001) and young (3.69 ± 0.23 to 5.86 ± 0.33; p <0.001) patients. After 14 weeks of oral diltiazem treatment, elimination half-life was slightly longer than at 2 weeks for the elderly (7.21 ± 0.64 vs 5.80 ± 0.48; p <0.03), but was not further prolonged in the young (6.34 ± 0.57 vs 5.65 ± 0.30; difference not significant), and no differences between groups were demonstrated at any of the 3 evaluations. Baseline plasma renin activity was lower in elderly patients (0.64 ± 0.21 vs 1.83 ± 0.22; p <0.002), but did not change during diltiazem treatment for either group. Plasma aldosterone and 24-hour urinary aldosterone excretion rate were unchanged with diltiazem treatment in both patient groups. These data suggest that diltiazem, administered as single drug therapy, is effective in the treatment of diastolic hypertension in both young and elderly hypertensive patients, it also decreased systolic blood pressure in elderly patients.