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Amlodipine: pharmacokinetic profile of a low-clearance calcium antagonist.

Structural features of amlodipine give the molecule physicochemical and pharmacokinetic properties that are unique among calcium antagonists. Amlodipine is absorbed gradually after oral administration (peak plasma levels 6-12 h postdose) and has an absolute bioavailability of 64%. Low clearance and a high volume of distribution give amlodipine a long elimination half-life, and mean effective plasma levels are maintained with once-daily doses. With repeated once-daily dosing, the steady state is achieved after the seventh to ninth dose. The pharmacokinetic properties of amlodipine avoid the sharp fluctuations in plasma level seen with other calcium antagonists that are associated with vasodilatation-induced side effects such as tachycardia, headache, and flushing. The pharmacokinetics of amlodipine are not significantly altered in elderly or renally impaired patients, but there is reduced clearance in patients with hepatic impairment. There are no pharmacokinetic interactions between amlodipine and cimetidine or digoxin.