Duration of Action of Verapamil in Hypertension
Immediate-release verapamil has a short duration of action requiring dosing 3 times daily, while sustained-release formulations provide long-acting blood pressure control with once-daily dosing. 1
Immediate-Release Verapamil
The immediate-release formulation has a short duration of action, necessitating administration 3 times daily at doses of 80-160 mg per dose. 1
- The mean elimination half-life ranges from 2.8 to 7.4 hours after single doses. 2
- With repetitive dosing, the half-life increases to 4.5 to 12.0 hours after less than 10 consecutive doses given 6 hours apart. 2
- Peak plasma concentrations are reached 1-2 hours after oral administration. 2
- The half-life may increase during titration, and aging can prolong elimination half-life in elderly patients. 2
Sustained-Release Verapamil
Sustained-release verapamil provides long-acting blood pressure control, allowing once-daily administration at doses of 120-480 mg. 1
- The sustained-release formulation maintains ambulatory blood pressure reduction throughout the 24-hour dosing interval when given once daily. 3
- In a study of 14 patients receiving 240 mg once daily, both clinic and mean ambulatory BP were significantly reduced by 17/12 and 16/8 mm Hg respectively, with this reduction maintained throughout the day. 3
- Mean 24-hour blood pressure control was achieved with sustained-release verapamil, with no statistically significant differences in blood pressure during awake versus sleep hours. 4
- Peak plasma verapamil concentration with sustained-release occurs at approximately 5.2 hours when fasting and 7.7 hours when taken with food. 2
Clinical Implications for Dosing
For optimal patient compliance and sustained blood pressure control, sustained-release verapamil dosed once daily is preferred over immediate-release formulations. 5, 3
- In long-term studies, 120 mg twice daily was as effective as 120 mg three times daily for blood pressure control, suggesting that less frequent dosing maintains efficacy. 5
- The antihypertensive effect is maintained during long-term treatment for up to 1 year without significant tachyphylaxis. 5, 6
- Dosage requirements vary between patients (80-360 mg daily), but once the effective dose is established with sustained-release formulations, once-daily administration maintains therapeutic effect. 4, 3
Important Pharmacokinetic Considerations
- Bioavailability of oral verapamil ranges from 20-35% due to extensive first-pass metabolism. 2
- In patients with hepatic insufficiency, elimination half-life is prolonged to 14-16 hours, and these patients may require only one-third of the normal daily dose. 2
- Approximately 90% is bound to plasma proteins, and about 70% is excreted as metabolites in urine within 5 days. 2