Immediate physiological effects of carvedilol are shown in a very short period of time. Within a few hours, even a small dose of carvedilol can lower blood pressure.1 It reaches peak plasma drug concentration in one to two hours, but is delayed by one to two hours when taken with food. Average terminal elimination half-life of carvedilol is around seven to ten hours.2 Absorption of the extended-release capsule form of carvedilol (Coreg CR) takes longer.3 It reaches peak concentration about 3.5 hours later than immediate-release carvedilol does,1 about five hours after administration,3 but maintains a stable concentration for 24 hours.4
Within one hour of administration, beta-blocking actions of carvedilol become evident.5 Alpha-mediated vasodilatory effects (decreased peripheral resistance and blood pressure) are seen within about 30 minutes of administration. A randomized, double-blinded, placebo-controlled trial studied 20 patients with mild to moderate essential hypertension.6 Systolic and diastolic blood pressure fell significantly 45 minutes after carvedilol administration. Mean blood pressure decreased from 126 ± 2.7 mm Hg before the treatment to 105.4 ± 5 mm Hg (p<0.01) at two hours after carvedilol administration. When patients were given daily treatment for four weeks, mean blood pressure also significantly decreased, from 126 ± 2.7 mm Hg before to 111.5 ± 4.2 mm Hg after treatment (p<0.01). Systolic and diastolic blood pressures significantly decreased by 13.7% and 13%, respectively. The placebo group’s blood pressure remained unchanged after acute or chronic treatment.
A different study observed that peak carvedilol blood levels were reached within 90 minutes.7 Systolic and diastolic blood pressure decreased by more than 7 mm Hg in 28 of 29 patients. Peak fall in blood pressure was about four hours after drug administration and always occurred after time to peak blood level. Another randomized, double-blinded, placebo-controlled study on patients with essential hypertension (n=20) showed that single dose of 50 mg of carvedilol reduced mean blood pressure (25/14mm Hg) significantly over a nine hour period.8,9
Acute effects of carvedilol included reduced heart rate and pulmonary artery and pulmonary wedge pressures in two days.10 Long term effects of carvedilol over a period of three months included increased rest and peak exercise cardiac, stroke volume, and stroke work indexes. Carvedilol also further reduced right atrial, pulmonary artery, and pulmonary wedge pressures, reduced heart failure symptoms, and improved submaximal exercise tolerance in patients with idiopathic cardiomyopathy.
References
- Stafylas PC, Sarafidis PA. Carvedilol in hypertension treatment. Vasc Health Risk Manag. 2008;4(1):23-30. 2008.
- Coreg [package insert]. Ciales, PR: GK Pharmaceuticals Contract Manufacturing Operations; 2008.
- Coreg CR [package insert]. Ciales, PR: GK Pharmaceuticals Contract Manufacturing Operations; 2008.
- Frishman WH, Henderson LS, Lukas MA. Controlled-release carvedilol in the management of systemic hypertension and myocardial dysfunction. Vasc Health Risk Manag. 2008;4(6):1387-1400.
- Vanderhoff BT, Ruppel HM, Amsterdam PB. Carvedilol: the new role of beta blockers in congestive heart failure. Am Fam Physician. 1998;58(7):1627-1634, 1641-1622.
- Dupont AG. Effects of carvedilol on renal function. Eur J Clin Pharmacol. 1990;38 Suppl 2:S96-100.
- Morgan T, Anderson A, Cripps J, Adam W. Pharmacokinetics of carvedilol in older and younger patients. J Hum Hypertens. 1990;4(6):709-715.
- Ruffolo RR, Boyle DA, Brooks DP, et al. Carvedilol: A novel cardiovascular drug with multiple actions. Cardiovasc Drug Rev. 1992;10(2):127-157.
- Dupont AG, Van der Niepen P, Taeymans Y, et al. Effect of carvedilol on ambulatory blood pressure, renal hemodynamics, and cardiac function in essential hypertension. J Cardiovasc Pharmacol. 1987;10 Suppl 11:S130-136.
- Metra M, Nardi M, Giubbini R, Cas LD. Effects of short- and long-term carvedilol administration on rest and exercise hemodynamic variables, exercise capacity and clinical conditions in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 1994;24(7):1678-1687.
