Clinical Pharmacokinetics of Amlodipine

Abstract

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.

All Thiazide‐Like Diuretics Are Not Chlorthalidone: Putting the ACCOMPLISH Study Into Perspective

“…It has a half-life of 38 to 50 hours and full 24-hour duration of action that maintains a trough:peak ratio of 57.7, even 72 hours following abrupt withdrawal. 15,16 Combining amlodipine with any other agent, including benazepril, easily carries the BP-lowering effect throughout the 24-hour period. With these characteristics in mind, it is surprising that the differences in BP reduction were not greater in favor of the amlodipine-benazepril combination than those actually observed in ACCOMPLISH.…”

Double-blind crossover study of the interaction between perindopril and amlodipine on blood pressure and hormones related to fluid and electrolyte balance in patients with essential hypertension

“…These changes were not significantly different from the corresponding observed in Group A was dependent upon pre-existing ACE inhibition. A potential pharmacokinetic effects of placebo (−0.7 and −1.8 mm Hg), whereas the changes with 4, 8 or 16 mg/day were greater than explanation is that amlodipine, which has a high affinity for protein, 21 might have displaced perindowith placebo. In this study, 6-h post-dose measurements were also made, and again showed changes prilat by non-specific binding to ACE.…”

Effects of Amlodipine on the Pharmacokinetics of Warfarin after Oral and Intravenous Administration of Warfarin in Rats

“…Amlodipine is rapidly absorbed and is extensively metabolized in the liver while it shows linear dose-related pharmacokinetic characteristics and, at steadystate, there are relatively small fl uctuations in plasma concentrations across a dosage interval (Abernethy, 1992). Although structurally related to other dihydropyridine derivatives, amlodipine displays signifi cantly different pharmacokinetic characteristics (Meredith et al, 1992). Amlodipine is a substrate of cytochrome P450 (CYP) 3A subfamily, specifi cally CYP3A4 (Nishio et al, 2005;Kim et al, 2009).…”