Pharmacotherapeutic Group: Anti-anginal Drug.
Pharmacology: Ranolazine may have some antianginal effects by inhibition of the late sodium current in cardiac cells. This reduces intracellular sodium accumulation and consequently decreases intracellular calcium overload. Ranolazine, via its action to decrease the late sodium current, is considered to reduce these intracellular ionic imbalances during ischaemia. This reduction in cellular calcium overload is expected to improve myocardial relaxation and thereby decrease left ventricular diastolic stiffness.
Pharmacokinetics: After oral administration of ranolazine, peak plasma concentrations (Cmax) are typically max observed between 2 and 6 hours. Steady state is generally achieved within 3 days of twice-daily dosing. The mean absolute bioavailability of ranolazine after oral administration of immediate-release ranolazine tablets ranged from 35-50%, with large inter-individual variability. There was a 2.5- to 3-fold increase in steady-state AUC as the dose was increased from 500 mg to 1000 mg twice daily. Approximately 62% of ranolazine is bound to plasma proteins. The mean steady-state volume of distribution (Vss) is about 180 l. Ranolazine is eliminated primarily by metabolism. Less than 5% of the dose is excreted unchanged in the urine and faeces. The elimination half-life is about 2-3 hours after intravenous administration. The terminal half-life at steady state after oral administration of ranolazine is about 7 hours, due to the absorption rate-limited elimination.