VARIABILITY IN THE PHARMACOKINETICS AND PHARMACODYNAMICS OF LOW-DOSE ASPIRIN IN HEALTHY MALE-VOLUNTEERS

Data describing the pharmacokinetics and pharmacodynamics of low dose aspirin (acetylsalicylic acid; ASA) are limited. This single-center st udy was designed to determine the rate and extent of oral absorption o f 80-mg ASA tablets in healthy, young male subjects and to assess the intra- and inter-subject variability of ASA pharmacokinetics and plate let aggregation effects. Ten subjects each received a single, open-lab el, oral 80-mg ASA dose on three separate days. Each dose was separate d by a 2-week washout interval. Blood samples for pharmacokinetic dete rminations of ASA and its metabolite, salicylic acid (SA) and platelet aggregation studies were obtained at scheduled timepoints before and up to 24 hours after each dose, Peak plasma ASA levels of 1 mu g/mL we re achieved within 30 minutes. Peak plasma SA levels of approximately 4 mu g/mL were attained in 1 hour. The terminal half-lives (t(1/2)) of ASA and SA were 0.4 and 2.1 hours, respectively Both ASA and SA pharm acokinetics and the platelet aggregation response to ASA exhibited con siderable intra- and inter-subject variability. Inhibition of platelet aggregation was found to relate with ASA area under the plasma concen tration versus time curve (AUC).