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Home » , , , » Pharmacology of Ranolazine
Pharmacology of Ranolazine
Saturday, March 31, 2012 Posted by Piscean

Pharmacology of Ranolazine


Indication For the treatment of chronic angina. It should be used in combination with amlodipine, beta-blockers or nitrates.
Pharmacodynamics Ranolazine has antianginal and anti-ischemic effects that do not depend upon reductions in heart rate or blood pressure. It is the first new anti-anginal developed in over 20 years.
Mechanism of action The mechanism of action of ranolazine is unknown. It does not increase the rate-pressure product, a measure of myocardial work, at maximal exercise. In vitro studies suggest that ranolazine is a P-gp inhibitor. Ranolazine is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia.
Absorption Absorption is highly variable. After oral administration of ranolazine as a solution, 73% of the dose is systemically available as ranolazine or metabolites. The bioavailability of oral ranolazine relative to that from a solution is 76%.
Volume of distribution Not Available
Protein binding 62%
Metabolism
Hepatic, metabolized mainly by CYP3A and to a lesser extent by CYP2D6. The pharmacologic activity of the metabolites has not been well characterized.
Route of elimination Ranolazine is metabolized rapidly and extensively in the liver and intestine; less than 5% is excreted unchanged in urine and feces.
Half life 7 hours
Clearance Not Available
Toxicity In the event of overdose, the expected symptoms would be dizziness, nausea/vomiting, diplopia, paresthesia, and confusion. Syncope with prolonged loss of consciousness may develop.

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