Effects of amlodipine, a long-acting dihydropyridine calcium antagonist in aging hypertension: Pharmacodynamics in relation to disposition

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Abstract
Pharmacodynamics and disposition of amlodipine, a dihydropyridine calcium antagonist, were compared between elderly and young patients with hypertension. Elderly (mean ± SD; age, 68 ± 3 years) and young (35 ± 5 years) patients received single intravenous amlodipine doses followed by oral administration once daily for a total of 12 weeks. After intravenous administration, elderly patients had prolonged elimination half‐life values (58 ±11 versus 42 ± 8 hours; p < 0.01) caused by decreased clearance (19 ± 5 versus 25 ± 7 L/hr; p < 0.01). After a 3‐months oral treatment washout period, half‐life tended to be prolonged in the elderly patients (69 ± 20 hours for the elderly patients versus 53 ± 14 hours for the young patients; difference not significant) and was not markedly different from the short‐term intravenous measurement. Both systolic and diastolic blood pressure were significantly decreased from baseline throughout the treatment period, with greater decreases in elderly patients for both systolic and diastolic pressure. When amlodipine plasma concentration was correlated to change in mean blood pressure after short‐term intravenous doses, elderly patients had a greater decrease than young patients at a given drug concentration. However, after long‐term oral administration, elderly and young patients had comparable decreases in mean blood pressure at a given drug concentration, and the increased antihypertensive effect in the elderly was associated with somewhat higher amlodipine plasma concentration. Amlodipine administered once daily is an effective antihypertensive agent in elderly patients and young patients with essential hypertension. Clinical Pharmacology and Therapeutics (1990) 48, 76–86; doi:10.1038/clpt.1990.120

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