Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Dexcel-Pharma Ltd., 7 Sopwith Way, Drayton Fields, Daventry, Northamptonshire, NN11 8PB, UK
Pharmacotherapeutic group: Platelet Aggregation Inhibitor excl. Heparin
ATC code: B01AC06
The antiplatelet effect of aspirin is largely unrelated to its systemic bioavailability and its duration of effect does not correlate with the presence of intact salicylic acid in the circulation. The antiplatelet effect is considered to be largely pre-systemic, associated with acetylation of platelet cyclo-oxygenase in the portal circulation.
Aspirin (acetylsalicylic acid) irreversibly acetylates platelet cyclo-oxygenase thereby inhibiting the biosynthesis of thromboxane, a potent vasoconstrictor and inducer of platelet aggregation. It also inhibits the action of cyclo-oxygenase in the vascular endothelial wall preventing the synthesis of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation.
However, as the endothelial cell is capable of synthesising new cyclo-oxygenase, whereas the platelet is not, the effect on thromboxane is longer lasting.
Due to the low dose enteric-coated formulation of Aspirin 75mg Gastro-Resistant Tablets acetylsalicylic acid is slowly released into the portal circulation and is deacetylated by the liver to inactive salicylate before reaching the systemic circulation. It is postulated that platelets passing through the portal circulation are exposed to acetylsalicylic acid concentrations sufficient to achieve effective thromboxane inhibition, while systemic prostacyclin synthesis remains essentially unaffected.
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400mg was taken within 8 hours before or within 30 minutes after immediate release aspirin dosing (81mg), a decreased effect of aspirin on the formation of thromboxane or platelet aggregation occurred. However, the limitations of these data and the uncertainties regarding extrapolation of ex-vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.
Aspirin is rapidly absorbed after oral administration of conventional release preparations, with some hydrolysis to salicylate before absorption. Absorption is delayed by the presence of food and is impaired in patients suffering migraine attacks.
Absorption is more rapid in patients with achlorhydria and also following administration of polysorbates and antacids. Plasma concentrations of the drug increase disproportionately to the dose; e.g. a 325 mg dose having a half-life of 2-3 hours and higher doses showing lower plasma concentrations in the presence of an increased half-life due to a disproportionate increase in the volume of distribution.
Aspirin is found in saliva, milk, plasma and synovial fluid at concentrations less than in blood and crosses the placenta. Salicylate/protein binding extensive. Aspirin/protein binding to a small extent. In the blood, rapid hydrolysis to salicylic acid; glucuronic acid/glycine conjugation to form glucuronides and salicyluronic acid. Salicylate reabsorbed by renal tubules in acid urine, and alkaline diuresis will increase the rate of excretion; 85% of dose excreted as free salicylate.
The absolute bioavailability of aspirin from Aspirin 75mg Gastro-Resistant Tablets (compared with intravenous aspirin solution) is approximately 25%.
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.
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