Pharmacotherapeutic group: Platelet aggregation inhibitors excluding heparin. ATC-Code: B01AC06.
Pharmacology: Pharmacodynamics: Aspirin inhibits platelet aggregation by blocking thromboxane A2 synthesis in platelets. Its mechanism of action is based on irreversible inhibition of cyclo-oxygenase (COX-1). This inhibitory effect is especially pronounced in platelets, because platelets are unable to resynthesize this enzyme. Aspirin is also thought to have other inhibitory effects on platelets. Thus, it is used for various vascular indications.
Aspirin belongs to the group of acidic nonsteroidal anti-inflammatory drugs with analgesic, antipyretic and anti-inflammatory properties.
Higher oral doses are used for the relief of pain and in minor febrile conditions, such as colds or influenza, for the reduction of temperature and relief of the joint and muscle pains, and in acute and chronic inflammatory disorders such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.
Pharmacokinetics: Absorption: Following oral administration, Aspirin is absorbed rapidly and completely from the gastro-intestinal tract. During and after absorption Aspirin is converted into its main active metabolite, salicylic acid. Maximal plasma levels are reached after 10 - 20 minutes for Aspirin and after 0.3-2 hours for salicylic acid, respectively.
Tablets (immediate-release): Cmax is reached after approximately 30 minutes for Aspirin and after 1.5 hours for salicylic acid, respectively, when administered under fasting conditions. Intake with food leads to comparable Cmax and AUC, but the time to Cmax is prolonged on average about 2.7-fold when taken together with food. However, due to the mechanistic relationship between the total plasma exposure of Aspirin and its inhibitory effect on platelet aggregation, the difference in the rate of absorption of Aspirin is not considered relevant for the chronic therapy with low dose Aspirin in order to accomplish adequate inhibition of platelet aggregation.
Distribution: Both Aspirin and salicylic acid are extensively bound to plasma proteins and are rapidly distributed throughout the body. Salicylic acid passes into breast milk and crosses the placenta (see Use in Pregnancy & Lactation).
Metabolism/Biotransformation: The parent drug Aspirin is converted into its main metabolite salicylic acid. The acetyl group of Aspirin begins to split off hydrolytically even during passage through the intestinal mucosa but mainly this process takes place in the liver. The main metabolite Salicylic acid is eliminated predominantly by hepatic metabolism. Its metabolites are salicyluric acid, salicylic phenolic glucuronide, salicylacyl glucuronide, gentisic acid, and gentisuric acid.
Elimination/Excretion/Linearity: The elimination kinetics of salicylic acid is dose-dependent, as metabolism is limited by liver enzyme capacity. The elimination half-life therefore varies from 2 to 3 hours after low doses to up to about 15 hours at high doses. Salicylic acid and its metabolites are excreted mainly via the kidneys. Available pharmacokinetic data of Aspirin do not indicate a clinical meaningful deviation from dose-proportionality in the dose range of 100 mg to 500 mg.