Felodipine - How It Works
Clinical pharmacology details from the US FDA-approved label: how Felodipine works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
Mechanism of Action Felodipine is a member of the dihydropyridine class of calcium channel antagonists (calcium channel blockers). It reversibly competes with nitrendipine and/or other calcium channel blockers for dihydropyridine binding sites, blocks voltage-dependent Ca ++ currents in vascular smooth muscle and cultured rabbit atrial cells, and blocks potassium-induced contracture of the rat portal vein. In vitro studies show that the effects of felodipine on contractile processes are selective, with greater effects on vascular smooth muscle than cardiac muscle. Negative inotropic effects can be detected in vitro , but such effects have not been seen in intact animals. The effect of felodipine on blood pressure is principally a consequence of a dose-related decrease of peripheral vascular resistance in man, with a modest reflex increase in heart rate (see Cardiovascular Effects ). With the exception of a mild diuretic effect seen in several animal species and man, the effects of felo
CLINICAL PHARMACOLOGY Mechanism of Action Felodipine is a member of the dihydropyridine class of calcium channel antagonists (calcium channel blockers).
It reversibly competes with nitrendipine and/or other calcium channel blockers for dihydropyridine binding sites, blocks voltage-dependent Ca ++ currents in vascular smooth muscle and cultured rabbit atrial cells, and blocks potassium-induced contracture of the rat portal vein.
In vitro studies show that the effects of felodipine on contractile processes are selective, with greater effects on vascular smooth muscle than cardiac muscle.
Negative inotropic effects can be detected in vitro , but such effects have not been seen in intact animals.
The effect of felodipine on blood pressure is principally a consequence of a dose-related decrease of peripheral vascular resistance in man, with a modest reflex increase in heart rate (see Cardiovascular Effects ).
With the exception of a mild diuretic effect seen in several animal species and man, the effects of felodipine are accounted for by its effects on peripheral vascular resistance.
Pharmacokinetics and Metabolism Following oral administration, felodipine is almost completely absorbed and undergoes extensive first-pass metabolism.
The systemic bioavailability of felodipine is approximately 20%.
Mean peak concentrations following the administration of felodipine extended-release tablets, USP are reached in 2.5 to 5 hours.
Both peak plasma concentration and the area under the plasma concentration time curve (AUC) increase linearly with doses up to 20 mg.
Felodipine is greater than 99% bound to plasma proteins.
Following intravenous administration, the plasma concentration of felodipine declined triexponentially with mean disposition half-lives of 4.8 minutes, 1.5 hours, and 9.1 hours.
The mean contributions of the three individual phases to the overall AUC were 15, 40 and 45%, respectively, in the order of increasing t 1/2 .
Following oral administration of the immediate-release formulation, the plasma level of felodipine also declined polyexponentially with a mean terminal t 1/2 of 11 to 16 hours.
The mean peak and trough steady-state plasma concentrations achieved after 10 mg of the immediate-release formulation given once a day to normal volunteers, were 20 and 0.5 nmol/L, respectively.
The trough plasma concentration of felodipine in most individuals was substantially below the concentration needed to effect a half-maximal decline in blood pressure (EC 50 ) [4 to 6 nmol/L for felodipine], thus precluding once-a-day dosing with the immediate-release formulation.
Following administration of a 10 mg dose of felodipine, the extended-release formulation, to young, healthy volunteers, mean peak and trough steady-state plasma concentrations of felodipine were 7 and 2 nmol/L, respectively.
Corresponding values in hypertensive patients (mean age 64) after a 20 mg dose of felodipine extended-release were 23 and 7 nmol/L.
Since the EC 50 for felodipine is 4 to 6 nmol/L, a 5 mg to 10 mg dose of felodipine extended-release in some patients, and a 20 mg dose in others, would be expected to provide an antihypertensive effect that persists for 24 hours (see Cardiovascular Effects below and DOSAGE AND ADMINISTRATION ).
The systemic plasma clearance of felodipine in young healthy subjects is about 0.8 L/min, and the apparent volume of distribution is about 10 L/kg.
Pharmacokinetics
Pharmacokinetics and Metabolism Following oral administration, felodipine is almost completely absorbed and undergoes extensive first-pass metabolism. The systemic bioavailability of felodipine is approximately 20%. Mean peak concentrations following the administration of felodipine extended-release tablets, USP are reached in 2.5 to 5 hours. Both peak plasma concentration and the area under the plasma concentration time curve (AUC) increase linearly with doses up to 20 mg. Felodipine is greater than 99% bound to plasma proteins. Following intravenous administration, the plasma concentration of felodipine declined triexponentially with mean disposition half-lives of 4.8 minutes, 1.5 hours, and 9.1 hours. The mean contributions of the three individual phases to the overall AUC were 15, 40 and 45%, respectively, in the order of increasing t 1/2 . Following oral administration of the immediate-release formulation, the plasma level of felodipine also declined polyexponentially with a mean terminal t 1/2 of 11 to 16 hours. The mean peak and trough steady-state plasma concentrations achieved after 10 mg of the immediate-release formulation given once a day to normal volunteers, were 20 and 0.5 nmol/L, respectively. The trough plasma concentration of felodipine in most individuals was substantially below the concentration needed to effect a half-maximal decline in blood pressure (EC 50 ) [4 to 6 nmol/L for felodipine], thus precluding once-a-day dosing with the immediate-release for