Amlodipine: an overview of its pharmacodynamic and pharmacokinetic properties

Amlodipine, a third-generation dihydropyridine calcium antagonist, has a mode of action and pharmacodynamic profile which are comparable to those of conventional compounds in this series, such as nifedipine. Its physicochemical behavior, however, appears to be somewhat different. A pKa value of 8.7 means that amlodipine is predominantly present in the ionized form at a physiologic pH. It possesses, therefore, a strong affinity for cell membranes. These phenomena apparently contribute to amlodipine's unique pharmacokinetic profile, which is characterized by almost complete absorption, late-peak plasma concentrations, high bioavailability, and slow hepatic biodegradation. This profile translates into potential clinical benefits by virtue of a slow onset of action and long duration of effect. The slow onset of action may explain why there seems to be very little reflex tachycardia and a lower incidence of vasodilator side effects when comparing amlodipine with conventional dihydropyridines. The slow elimination of amlodipine explains the long duration of action, which allows a convenient once-daily dosage schedule.