Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers

• Published in: Clinical pharmacology: advances and applications 2014-01, Vol.6 (default), p.51-59
• Main Authors: Nagelschmitz, J, Blunck, M, Kraetzschmar, J, Ludwig, M, Wensing, G, Hohlfeld, T
• Format: Article
• Language: English
• Subjects: Acids; Acute coronary syndromes; Angina pectoris; Aspirin; Biosynthesis; Blood platelets; Cardiovascular disease; Chromatography; Coronary vessels; Dosage and administration; Drug dosages; Emergency medical care; Heart attacks; Original Research; Pharmacodynamics; Pharmacokinetics
• ISSN: 1179-1438; 1179-1438
• DOI: 10.2147/CPAA.S47895

The pharmacology of single doses of acetylsalicylic acid (ASA) administered intravenously (250 or 500 mg) or orally (100, 300, or 500 mg) was evaluated in a randomized, placebo-controlled, crossover study. Blood and urine samples were collected before and up to 24 hours after administration of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of platelet aggregation were determined using validated techniques. A comparison between administration routes showed that the geometric mean dose-corrected peak concentrations (Cmax/D) and the geometric mean dose-corrected area under the curve (AUC0-∞/D) were higher following intravenous administration of ASA 500 mg compared with oral administration (estimated ratios were 11.23 and 2.03, respectively). Complete inhibition of platelet aggregation was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid onset of inhibition that was not observed with oral dosing. At 5 minutes after administration, the mean reduction in arachidonic acid-induced thromboxane B2 synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500 mg intravenously. In exploratory analyses, thromboxane B2 synthesis was significantly lower after intravenous versus oral ASA 500 mg (P