Ecosprin Plus Mechanism of Action

Pharmacology: Clopidogrel bisulfate + Aspirin (Ecosprin Plus) is a fixed-dose combination containing Aspirin and Clopidogrel. Aspirin is an antiplatelet agent. It is an acetylsalicylic acid. Aspirin acts by causing irreversible inhibition of the cyclo-oxygenase enzyme, which leads to decreased formation of Thromboxane A2. Since platelets do not synthesize new enzyme, the action of Aspirin on platelet cyclo-oxygenase is permanent, lasting for the life of the platelets (7-10 days). Clopidogrel is a thienopyridine derivative that selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the GP llb/llla complex, thereby inhibiting platelet aggregation.
Pharmacokinetics: Clopidogrel is rapidly but incompletely absorbed after oral doses; absorption appears to be at least 50%. It is a prodrug and is extensively metabolized in the liver, mainly to the inactive carboxylic acid derivative; metabolism is mediated by the cytochrome P450 isoenzymes CYP3A4 and CYP2B6, and to a lesser extent by CYP1A2, CYP1A1 and CYP2C19. The active metabolite appears to be a thiol derivative; it has been identified in vitro but appears to be too unstable to be isolated from plasma. Clopidogrel and the carboxylic acid derivative are highly protein bound. Clopidogrel and its metabolites are excreted in urine and in faeces; about 50% of an oral dose is recovered from the urine and about 46% from the faeces.
Aspirin and other salicylates are absorbed rapidly from the gastrointestinal tract when taken orally but absorption after rectal doses is less reliable. Aspirin and other salicylates can also be absorbed through the skin.
After oral doses, absorption of non-ionised aspirin occurs in the stomach and intestine. Some aspirin is hydrolyzed to salicylate in the gut wall. Once absorbed, aspirin is rapidly converted to salicylate, but during the first 20 minutes after an oral dose aspirin is the main form of the drug in the plasma. Aspirin is 80 to 90% bound to plasma proteins and is widely distributed; its volume of distribution is reported to be 170 mL/kg in adults. As plasma-drug concentrations increase, the binding sites on the proteins become saturated and the volume of distribution increases. Both aspirin and salicylate have pharmacological activity although only aspirin has an anti-platelet effect. Salicylate is extensively bound to plasma proteins and is rapidly distributed to all body parts. Salicylate appears in breast milk and crosses the placenta.