Amlodipine is a dihydropyridine calcium antagonist drug with distinctive pharmacokinetic characteristics which appear to be attributable to a high degree of ionisation. Following oral administration, bioavailability is 60 to 65% and plasma concentrations rise gradually to peak 6 to 8h after administration. Amlodipine is extensively metabolised in the liver (but there is no significant presystemic or first-pass metabolism) and is slowly cleared with a terminal elimination half-life of 40 to 50h. Volume of distribution is large (21 L/kg) and there is a high degree of protein binding (98%). There is some evidence that age, severe hepatic impairment and severe renal impairment influence the pharmacokinetic profile leading to higher plasma concentrations and longer half-lives. There is no evidence of pharmacokinetic drug interactions. Amlodipine shows linear dose-related pharmacokinetic characteristics and, at steady-state, there are relatively small fluctuations in plasma concentrations across a dosage interval.
Thus, although structurally related to other dihydropyridine derivatives, amlodipine displays significantly different pharmacokinetic characteristics and is suitable for administration in a single daily dose.
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Meredith, P.A., Elliott, H.L. Clinical Pharmacokinetics of Amlodipine. Clin-Pharmacokinet 22, 22–31 (1992). https://doi.org/10.2165/00003088-199222010-00003
- Cardiovascular Pharmacology
- Severe Hepatic Impairment