Half-life of Amlodipine
The half-life of amlodipine is approximately 30 to 50 hours, making it one of the longest-acting calcium channel blockers available. 1
Pharmacokinetic Profile
Amlodipine has distinctive pharmacokinetic properties that contribute to its clinical utility:
- After oral administration, absorption produces peak plasma concentrations between 6 and 12 hours
- Absolute bioavailability ranges between 64% and 90%
- Elimination from plasma is biphasic with a terminal elimination half-life of about 30-50 hours 1
- Steady-state plasma levels are reached after 7-8 days of consecutive daily dosing 1
- Approximately 93% of circulating drug is bound to plasma proteins 1
The long half-life of amlodipine (30-50 hours) provides several clinical advantages:
- Allows for once-daily dosing
- Provides consistent 24-hour blood pressure control
- Results in small peak-to-trough variations in plasma drug levels (only 20-25% fluctuation) 2
- Reduces the incidence of early vasodilator side effects 3
Special Populations
The pharmacokinetics of amlodipine are affected in certain populations:
- Elderly patients have decreased clearance with a resulting increase in AUC of approximately 40-60% 1
- Patients with hepatic insufficiency also have decreased clearance with similar increases in AUC 1
- Renal impairment does not significantly influence the pharmacokinetics of amlodipine 1
Clinical Implications
The long half-life of amlodipine has important clinical implications:
- Provides effective 24-hour control of hypertension with once-daily dosing 4
- Maintains the normal circadian pattern of blood pressure changes 5
- Allows for gradual onset of effect, reducing the risk of reflex tachycardia 2
- After discontinuation, blood pressure returns to baseline gradually over 7-10 days, with no evidence of rebound hypertension 2
Comparison to Other Calcium Channel Blockers
Amlodipine's half-life is significantly longer than other calcium channel blockers:
- Eplerenone has a shorter half-life, requiring twice-daily administration for optimal effect 6
- Amlodipine's long half-life (30-50 hours) contributes to its superior 24-hour blood pressure control compared to other dihydropyridine calcium channel blockers 7
This extended half-life is a key factor in amlodipine's continued prominence as a first-line antihypertensive agent, even with the development of newer calcium channel blockers.