Nicardipine Aguettant

Nicardipine Aguettant Mechanism of Action



Laboratoire Aguettant


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Full Prescribing Info
Pharmacotherapeutic group: Selective calcium inhibitors with vascular effects. ATC code: C08CA04 (cardiovascular system).
Pharmacology: Pharmacodynamics: Mechanism of action: Nicardipine is a second generation slow calcium channel inhibitor, and belongs to the phenyl-dihydropyridine group. Nicardipine 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).
Pharmacodynamic effects: Administered by systemic route, nicardipine 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 is highly bound to plasma proteins over a wide concentration range.
Biotransformation: Nicardipine is metabolised 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 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.
Elimination: After co-administration of a radioactive intravenous dose of nicardipine with an oral 30 mg dose given every 8 hours, 49% of the radioactivity was recovered in the urine and 43% in the faeces within 96 hours. None of the dose was recovered as unchanged nicardipine in the urine. The elimination profile of the medicinal product 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 failure: The pharmacokinetics of intravenously administered nicardipine was studied in subjects with severe renal failure requiring haemodialysis (creatinine clearance <10 ml/min), mild/moderate renal failure (creatinine clearance 10-50 ml/min) and normal renal function (creatinine clearance >50 ml/min). At steady state, Cmax and AUC were significantly higher and clearance significantly lower in subjects with mild/moderate renal failure compared with subjects with normal renal function. There were no significant differences in the principal pharmacokinetic parameters between severe renal dysfunction and normal renal function.
Toxicology: Preclinical safety data: Nicardipine has been shown to pass into the milk of lactating animals. It has been reported in animal studies that the medicinal product is excreted into breast milk. In animal studies where this medicinal product was administered at a high dose during the terminal stage of pregnancy, an increase in foetal deaths, delivery disturbances, decrease in the body weight of offspring, and suppression of post-natal body weight gain were reported. However, toxicity to reproduction has not been reported.
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