Nicardin Mechanism of Action

Pharmacotherapeutic Class: Selective calcium inhibitors with vascular effects. ATC Code: C08CA04.
Pharmacology: Pharmacodynamics: Nicardipine hydrochloride (Nicardin) is a second generation slow calcium channel inhibitor, and belongs to the phenyl-dihydropyridine group.
Nicardipine hydrochloride (Nicardin) has a greater selectivity for L-type calcium channels in vascular smooth muscle than cardiac myocytes. At very low concentrations it inhibits the influx of calcium into the cell. Its action is produced mainly on arterial smooth muscle. This is reflected in relatively large and rapid changes in blood pressure, with minimal inotropic changes in cardiac function (baroreflex effect).
Administered by systemic route, Nicardipine hydrochloride (Nicardin) is a potent vasodilator which diminishes total peripheral resistance and lowers blood pressure. Heart rate is temporarily increased; as a result of a decrease in after-load, cardiac output is markedly and durably increased.
In humans, the vasodilator action also occurs in both acute dose administration and chronic administration in the large and small arteries, increasing blood flow and improving arterial compliance. Renal vascular resistance is decreased.
Pharmacokinetics: Distribution: Nicardipine hydrochloride (Nicardin) is highly protein bound in human plasma over a wide concentration range.
Metabolism: Nicardipine hydrochloride (Nicardin) is metabolized by cytochrome P450 3A4. Studies involving either a single dose, or administration 3 times daily for 3 days, have shown that less than 0.03% of unchanged Nicardipine hydrochloride (Nicardin) is recovered in the urine in humans after oral or intravenous administration. The most abundant metabolite in human urine is the glucuronide of the hydroxy form, which is formed by the oxidative cleaving of the N-methylbenzyl moiety and the oxidation of the pyridine ring.
Excretion: After co-administration of a radioactive intravenous dose of Nicardipine hydrochloride (Nicardin) with an oral 30 mg dose given every 8 hours, 49% of the radioactivity was recovered in the urine and 43% in the feces within 96 hours. None of the dose was recovered as unchanged Nicardipine hydrochloride (Nicardin) in the urine. The elimination profile of the drug following an intravenous dose consists of three phases, with corresponding half-life: alpha 6.4 min, beta 1.5 hours, gamma 7.9 hours.
Renal impairment: The pharmacokinetics of intravenously administration of Nicardipine hydrochloride (Nicardin) was studied in subjects with severe renal dysfunction requiring hemodialysis (creatinine clearance <10 mL/min), mild/moderate renal dysfunction (creatinine clearance 10-50 mL/min) and normal renal function (creatinine clearance >50 mL/min). At steady state, Cmax (the maximum concentration of a drug in the body after dosing) and AUC (area under the curve) were significantly higher and clearance is significantly lower in subjects with mild/moderate renal function compared with in subjects with normal renal function. There were no significant differences in the principal pharmacokinetic parameters between severe renal dysfunction and normal renal dysfunction.