Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Nervous system, other analgesics and antipyretics, salicylic acid and derivatives.
ATC code: N02BA01

Acetylsalicylic acid is a member of the class of acid-forming non-steroidal anti-inflammatory drugs with analgesic, antipyretic and anti-inflammatory properties. Its mechanism of action is based on irreversible inhibition of cyclooxygenase enzymes involved in prostaglandin synthesis.

Acetylsalicylic acid is used at oral doses of between 0.3 and 1.0 g to treat mild to moderate pain and fever, e.g. associated with colds or flu, to lower fever and to treat joint and muscle pain.

It is also used to treat acute and chronic inflammatory diseases such as rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.
Acetylsalicylic acid also inhibits platelet aggregation by blocking the synthesis of thromboxane A2 in platelets. For this reason, doses of 75 to 300 mg daily are used in various cardiovascular indications.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
Acetylsalicylic acid is absorbed rapidly and completely from the gastrointestinal tract following oral administration. During and after absorption acetylsalicylic acid is converted into its main active metabolite, salicylic acid. Peak plasma levels of acetylsalicylic acid and salicylic acid are reached after 18 - 30 minutes and 0.72–2 hours, respectively. The given durations depend on the pharmaceutical form.
For Aspirin (500 mg tablets), the active substance acetylsalicylic acid has mean peak plasma concentrations (Cmax) of 5.4 µg/mL; mean time to peak plasma concentrations (Tmax) is 30 min; mean total exposure to acetylsalicylic acid (area under the curve/AUC) is 6.2 µg x h/mL.
For salicylic acid, mean peak plasma concentrations (Cmax) are 25.4 µg/mL; mean time to peak plasma concentrations (Tmax) is 2 h; mean total exposure (area under the curve/AUC) is 145 µg x h/mL.
Both acetylsalicylic acid 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.
Acetylsalicylic acid is converted into its main metabolite, salicylic acid. The acetyl group of the acetylsalicylic acid starts being cleaved by hydrolysis as it passes through the intestinal mucosa. This process takes place primarily in the liver. The metabolites of salicylic acid are salicyluric acid, salicyl phenolic glucuronide, salicyl acyl glucuronide, gentisic acid and gentisuric acid.
The elimination kinetics of salicylic acid are dose-dependent, as metabolism is limited by hepatic enzyme capacity. The elimination half-life therefore varies from 2 to 3 hours after low doses to about 15 hours after high doses. Salicylic acid and its metabolites are excreted primarily via the kidneys.