Half-Life of Amlodipine
Amlodipine has a terminal elimination half-life of approximately 30-50 hours, which is one of the longest among calcium channel blockers and enables true once-daily dosing with sustained blood pressure control. 1
Pharmacokinetic Profile
The elimination characteristics of amlodipine are distinctive among dihydropyridine calcium antagonists:
- The terminal elimination half-life ranges from 30-50 hours in patients with normal hepatic function 1
- The elimination half-life extends to 40-60 hours in some studies, with steady-state plasma levels reached after 7-8 days of consecutive daily dosing 2
- This slow elimination rate results from amlodipine being a low-clearance drug with extensive hepatic metabolism (approximately 90% converted to inactive metabolites) 1, 2
Clinical Implications of the Long Half-Life
The extended half-life confers several clinically relevant characteristics:
- Plasma concentration fluctuation between doses is only 20-25% with once-daily dosing, providing stable drug levels throughout the 24-hour period 2
- Blood pressure control is maintained for more than 24 hours following a single dose, offering protection even if a dose is missed 3
- In chemical adherence testing, amlodipine can remain analytically positive up to a week after the last ingestion, making it difficult to distinguish between regular and sporadic dosing 4
- Discontinuation results in a gradual return of blood pressure to baseline over 7-10 days with no rebound effect 2, 5
Special Populations
The half-life is significantly affected by hepatic function:
- In patients with hepatic insufficiency, the plasma elimination half-life extends to 56 hours, requiring dose titration and potentially lower initial doses 1
- Elderly patients experience decreased clearance with a 40-60% increase in AUC, though the specific half-life extension is not quantified 1
- Renal impairment does not significantly influence amlodipine pharmacokinetics, as only 10% of the parent compound is excreted renally 1
Comparison to Other Calcium Channel Blockers
The half-life of amlodipine is substantially longer than other dihydropyridines:
- Amlodipine demonstrates more effective nighttime blood pressure control compared to felodipine extended-release, likely due to its longer elimination half-life 6
- This extended half-life distinguishes amlodipine from shorter-acting calcium antagonists and contributes to its gradual onset of action (peak plasma concentration at 6-12 hours) 1, 2
Overdose Considerations
The long half-life has important implications in overdose situations:
- Amlodipine overdose produces prolonged hemodynamic effects requiring extended clinical monitoring 7
- In a reported case, serum amlodipine concentration remained elevated at 79 ng/mL even 35 hours after ingestion, demonstrating the drug's persistence 7
- Patients with amlodipine overdose require aggressive decontamination therapy and may need extended supportive care if hemodynamically unstable 7