What is the effect of Amlodipine 2.5mg during the trough period, especially in the last hours?

Amlodipine 2.5mg Trough Effect and Last-Hour Coverage

Amlodipine 2.5mg maintains effective blood pressure control throughout the entire 24-hour dosing interval, including the trough period in the last hours before the next dose, due to its exceptionally long elimination half-life of 40-60 hours. 1

Pharmacokinetic Profile Supporting Trough Coverage

Amlodipine's unique pharmacokinetic properties ensure minimal fluctuation between peak and trough levels:

• The elimination half-life of 40-60 hours results in only 20-25% fluctuation in plasma drug concentration between doses with once-daily administration 1
• Peak plasma concentrations occur 6-8 hours after dosing, with gradual onset of effect that prevents reflex tachycardia 1
• Steady-state is achieved over 1-1.5 weeks of once-daily dosing, with no tendency for drug accumulation even in patients with renal dysfunction 1, 2

Blood Pressure Control During Trough Period

Clinical evidence demonstrates sustained antihypertensive effect throughout the 24-hour dosing interval:

• In clinical trials, maintenance of blood pressure effect over the entire 24-hour dosing interval was observed, with little difference between peak and trough effect 3
• Ambulatory blood pressure monitoring studies show significant reductions in all time periods including the last six-hour dosing interval 4
• The JNC 7 guidelines specifically note that blood pressure should be measured just prior to dosing to determine if satisfactory control is obtained, and that amlodipine is dosed once daily 5

Trough Effect Considerations

While amlodipine generally maintains 24-hour coverage, monitoring for trough effect is still recommended:

• The JNC 7 guidelines acknowledge that "in some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval (trough effect)" 5
• If inadequate trough control is identified, an increase in dosage (from 2.5mg to 5mg or 10mg) should be considered rather than increasing frequency 5
• The usual dose range for amlodipine is 2.5-10mg once daily, with 2.5mg being the minimum effective dose 5, 6

Evidence Against Divided Dosing

Dividing amlodipine doses provides no additional benefit:

• A crossover study comparing amlodipine 10mg once daily versus 5mg twice daily found no significant differences in 24-hour, daytime, nighttime, or early morning blood pressure control 7
• Trough plasma amlodipine concentrations were not significantly different between once-daily and twice-daily administration (20.57 vs 22.37 ng/mL) 7
• The long half-life makes divided dosing pharmacologically unnecessary 1, 7

Clinical Monitoring Recommendations

To assess trough coverage adequacy:

• Measure blood pressure just prior to the next scheduled dose to evaluate trough control 5
• Consider 24-hour ambulatory blood pressure monitoring if trough effect is suspected, particularly evaluating early morning blood pressure before dosing 4
• If blood pressure goal is not met at trough, titrate upward to 5mg or 10mg once daily rather than splitting doses 5, 6

Special Populations

Amlodipine 2.5mg maintains efficacy in specific patient groups:

• In pediatric patients aged 6-17 years, 2.5mg once daily is the recommended starting dose with demonstrated efficacy 5, 3
• In patients with renal dysfunction, amlodipine 2.5-5mg daily maintains efficacy without drug accumulation or significant worsening of renal function 2
• In elderly patients, dose initiation should be low and titrated cautiously, but once-daily dosing remains appropriate 5