Pharmacokinetics and Pharmacodynamics of Amlodipine

Abstract

Amlodipine is a low-clearance, dihydropyridine calcium antagonist. The slow rate of elimination (elimination half-life of 40-60 h) confers several pharmacokinetic characteristics that are not seen with other calcium-antagonist drugs. It has high oral bioavailability (60-80%) and accumulates to a steady-state with once-daily administration over a period of 1-1 ½ weeks. Fluctuation of plasma drug concentration between doses is between 20 and 25% when once-daily dosing is used. Onset of effect is gradual after oral administration which is due, in part, to an intermediate rate of drug absorption (peak plasma drug concentration occurs 6-8 h after dosing) and perhaps also to the physicochemical characteristics of the drug-cell membrane-receptor interaction. The pharmacodynamic profile of the drug in hypertensive patients is consistent with the disposition of the drug. After single doses, blood pressure decreases gradually over 4-8 h and may slowly return to baseline over 24-72 h. No change in heart rate is noted after the dose as the onset is gradual and physiological reflexes are not activated. During chronic, oral, once-daily dosing blood pressure is decreased from pretreatment baseline with little fluctuation over the 24-hour dose interval. Discontinuation of amlodipine treatment results in a slow return of blood pressure to baseline over 7-10 days, with no evidence of a ‘rebound’ effect. Amlodipine is a low-clearance, dihydropyridine calcium antagonist which is effective for the treatment of hypertension and angina pectoris with once-daily dosing.