Amlodipine in elderly hypertensive patients: Pharmacokinetics and pharmacodynamics

Elderly (65-73 years) and young (28-34) hypertensive patients received amlodipine by i.v. infusion (2.5, 5.0, or 10.0 mg). Patients were then started on oral amlodipine 2.5 mg daily for 2 weeks, at the end of which amlodipine disposition and effect were evaluated over one 24-h dose interval. Patients were treated subsequently with amlodipine in an escalating dose protocol (maximum 10.0 mg once daily) for 12 weeks to control blood pressure. After i.v. amlodipine, clearance tended to be decreased in elderly as compared with young patients with resulting prolongation in elimination half-life (64 ± 20 vs. 48 ± 8 h; mean ± SD). Maximum decrease in systolic blood pressure (SBP) after i.v. doses tended to be greater in the elderly (-34 ± 15 vs. -23 ± 15 mm Hg) and maximum decrease in diastolic blood pressure (DBP) was similar in the two groups (-21 ± 10 vs. -18 ± 7 mm Hg). SBP was significantly decreased after 14 weeks' therapy in the elderly at doses ranging from 2.5 to 10.0 mg per day (171 ± 17 to 149 ± 22 mm Hg; p < 0.01). DPB was decreased both at 2 and 14 weeks' therapy in the elderly (baseline 100 ± 7, 2 weeks 93 ± 5, 14 weeks 90 ± 5 mm Hg; p < 0.01 vs. baseline). Similar decreases in DBP were noted in young patients (baseline 96 ± 6,2 weeks 81 ± 15, 14 weeks 84 ± 15 mm Hg). Humoral measures at baseline (pretreatment), 2 weeks' therapy, and 14 weeks' therapy were as follows: norepinephrine (640, 498, 454 pg/ml; NS), epinephrine (70, 59, 60 pg/ml; NS), plasma renin activity (1.5, 1.8, 2.0 ng ml^-1 h^-1; NS) urinary aldosterone excretion rate (11.4, 13.4, 11.0 μg/24 h; NS), and plasma atrial natriuretic factor (71.1, 80.4, 68.3 pg/ml; NS). Amlodipine clearance tends to be decreased in elderly patients, suggesting increased drug accumulation during chronic dosing. No obvious drug-related side effects were noted in any patient. Amlodipine is effective as single-drug therapy in the treatment of both systolic and diastolic hypertension in the elderly and diastolic hypertension in younger patients.