KLINISCHE PHARMAKOLOGIE VON ACETYLSALIZYLSAURE

The pharmacological actions of acetylsalicylic acid (ASA) are determined by two compounds: ASA and salicylic acid. Salicylic acid is formed from its precursor ASA within 15-20 min after oral application and is responsible for the antiinflammatory, antipyretic, and analgetic activities of ASA. However, the platelet inhibitory, i.e., the antithrombotic action of ASA is only due to this compound itself and is caused by irreversible inhibition of the platelet cyclooxygenase, i.e., inhibition of thromboxane A₂ formation. The bioavailability of plain ASA after oral administration amounts to 40-50% at therapeutic doses. This is due to rapid deacetylation prior to reaching the systemic circulation. This deacetylation accounts for a significant part of inhibition of platelet cyclooxygenase within the portal circulation which is further enhanced by using sustained-release preparations. Doses of 40-50 mg ASA per day are sufficient to maintain complete blockade of platelet cyclooxygenase and this agrees well with the established efficacy of 75 mg ASA/day in controlled clinical trials on secondary prevention of myocardial infarction.