Cardimed Mechanism of Action

Pharmacology: Nicardipine inhibits the transmembrane influx of calcium ions into cardiac muscle and smooth muscle without changing serum calcium concentrations. The contractile processes upon the movement of extracellular calcium ions into these cells through specific ion channels. The effects of Nicardipine are more selective to vascular smooth muscle than cardiac muscle. In animal models, Nicardipine produced relaxation of coronary vascular smooth muscle at drug levels which cause little or no negative inotropic effect.
Pharmacokinetics: Following infusion, Nicardipine plasma concentrations decline tri-exponentially, with a rapid early distribution phase (a half life of 2.7 minutes), an intermediate phase (β-half-life of 44.8 minutes), and a slow terminal phase (y-half-life of 14.4 hours) that can only be detected after long-term infusions. Total plasma clearance (Cl) is 0.4 L/hr/kg, and the apparent volume of distribution (Vd) using a non-compartment model is 8.3 L/kg. The pharmacokinetics of Nicardipine hydrochloride injection are linear over the dosage range of 0.5 to 40 mg/hr.
Rapid dose-related increases in Nicardipine plasma concentrations are seen during the first two hours after the start of an infusion of Nicardipine hydrochloride injection. Plasma concentrations increase at much slower rate after the first few hours, and approach steady state at 24 to 48 hours. On termination of infusion, Nicardipine concentrations decrease, with at least a 50% decrease during the first two hours post-infusion. The effects of Nicardipine on blood pressure significantly correlate with plasma concentrations.
Nicardipine is highly protein bound (>95%) in human plasma over a wide concentration range.
Nicardipine hydrochloride injection has been shown to be rapidly and extensively metabolized by the liver. After coadministration of a radioactive intravenous dose of Nicardipine hydrochloride injection 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. Nicardipine does not include or inhibits its own metabolism and does not induce or inhibit hepatic microsomal enzymes. The steady-state pharmacokinetics of Nicardipine are similar in elderly hypertensive patients (>65 years) and young healthy adults.