Amlodipine Onset of Action
Amlodipine begins lowering blood pressure within 6-12 hours after the first dose, with peak plasma concentrations and maximum blood pressure reduction occurring 6-12 hours post-administration, though full antihypertensive effect develops gradually over several days to weeks. 1
Pharmacokinetic Timeline
Immediate Effects (First Dose)
- Peak plasma concentrations occur 6-12 hours after oral administration, with absorption producing a gradual rise in drug levels 1
- Blood pressure begins decreasing gradually over 4-8 hours after a single dose 2
- The gradual onset is due to intermediate absorption rate and physicochemical characteristics of the drug-receptor interaction 2
Early Treatment Period (Days 1-7)
- After single doses, blood pressure may slowly return toward baseline over 24-72 hours, indicating incomplete effect from a single dose 2
- Steady-state plasma levels are reached after 7-8 days of consecutive daily dosing, when full therapeutic effect is achieved 1
- The long elimination half-life of 30-50 hours allows drug accumulation over the first week 1
Established Therapy (Week 2 and Beyond)
- Once steady-state is reached, antihypertensive effectiveness is maintained for at least 24 hours with once-daily dosing 1
- Plasma concentrations fluctuate only 20-25% between doses at steady state 2
- Blood pressure control persists even if a dose is missed, providing protection against incidental non-adherence 3
Clinical Implications
Advantages of Gradual Onset
- The gradual onset avoids dangerous rapid blood pressure drops and reflex tachycardia, unlike immediate-release nifedipine 4, 5
- No significant change in heart rate occurs after dosing because physiological reflexes are not activated 2
- Reduced incidence of side effects such as headache and flushing compared to other calcium antagonists 5
Dosing Considerations
- Initial dose of 5 mg once daily is appropriate for most adults, with assessment for dose escalation to 10 mg after 2-6 weeks if blood pressure remains above target 6
- In elderly patients, clearance is decreased and elimination half-life is prolonged (64 vs 48 hours), but therapeutic effect is maintained with standard dosing 7
- The drug can be administered at any convenient time of day to improve adherence 6
Duration of Effect
- Upon discontinuation, blood pressure slowly returns to baseline over 7-10 days with no rebound effect 2
- This prolonged offset provides a safety margin if treatment is interrupted 2
Common Pitfall to Avoid
Do not expect immediate blood pressure control or assess treatment failure too early. Clinicians should wait at least 7-8 days for steady-state to be achieved before judging efficacy, and typically 2-6 weeks before considering dose escalation 6, 1. The gradual pharmacokinetic profile is a therapeutic advantage, not a limitation, as it provides sustained 24-hour control with excellent tolerability 2, 3.