Clin Pharmacokinet 2003; 42 (12): 1059-1070 ORIGINAL RESEARCH ARTICLE 0312-5963/03/0012-1059/$30.00/0  Adis Data Information BV 2003. All rights reserved. Pharmacokinetic and Pharmacodynamic Differences Between Two Low Dosages of Aspirin May Affect Therapeutic Outcomes Chiara Cerletti, 1 Giuseppe Dell’Elba, 1 Stefano Manarini, 1 Romina Pecce, 1 Augusto Di Castelnuovo, 2 Nicola Scorpiglione, 3 Vincenzo Feliziani 3 and Giovanni de Gaetano 4 1 ‘G. Bizzozero’ Laboratory of Blood and Vascular Cell Interactions, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy * 2 ‘A. Valenti’ Laboratory of Genetics and Environmental Risk Factors for Thrombotic Disease, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy 3 ‘F. Renzetti’ Hospital, Lanciano, Italy 4 Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy Background: Meta-analyses of the prevention of major vascular events by aspirin Abstract suggest therapeutic equivalence of all dosages. However, the optimal dosage still remains problematic, and a recent trial found aspirin 160 mg/day to be more effective than 80 mg/day for secondary prevention of ischaemic stroke. Objective: To evaluate two low dosages of aspirin in terms of pharmacokinetics and pharmacodynamics (inhibition of platelet thromboxane generation and urin- ary excretion of thromboxane and prostacyclin metabolites). Design and Participants: A randomised cross-over study was performed in 16 healthy volunteers (9 women and 7 men, 33.8 α 5.1 years old) given enteric-coat- ed aspirin 80 or 160 mg/day for 7 days. Methods: Plasma concentrations of salicylate and aspirin were measured by high-performance liquid chromatography (HPLC) after both the first and the last dose (days 1 and 7). The usual pharmacokinetic parameters were then derived. Serum thromboxane B2 (TxB2) was measured by radioimmunoassay. The urinary excretion of 11-dehydro-TxB2 and 2,3-dinor-6-keto-prostaglandin F1× were mea- sured on 8-hour urine samples by immunoassay after extraction and HPLC separation, both before and after 7 days of drug administration. Results: With the 160mg dosage, but not with the 80mg dosage, higher concentra- tions of aspirin were found at day 7 compared with day 1. For aspirin 80 mg/day, 24-hour area under the concentration-time curve (AUC24) was similar on days 1 and 7 (569 α 339 vs 605 α 377 g h/L), but increased from 904 α 356 g h/L on day 1 to 1355 α 883 g h/L on day 7 with the higher dosage. Similarly, the * At the time of publication Dr Cerletti is affiliated with the Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy.