Maddalena Padrini1, Luca Spiezia2, Giovanni De Rosa3, Paolo Simioni2, Ornella Milanesi1 and Roberto Padrini3*
1Department of Women’s and Children’s Health, Pediatric Cardiology Unit, University of Padova, Italy 2Department of Medicine, Thrombotic, Hemorrhagic and Coagulation Diseases Unit, University of Padova, Italy 3Department of Medicine, Clinical Pharmacology Unit, University of Padova, ItalyFulltext PDF
Objective: To investigate pharmacodynamic and pharmacokinetic variability of aspirin in children and adolescents on antithrombotic prophylaxis for cardiac diseases. Methods: Twenty-nine patients, aged between 6 months and 18 years, on stable Aspirin (ASA) treatment for at least one week were the study population. At 4, 5 and 6 hours after drug administration blood samples were collected to assay plasma concentrations of ASA and Salicylic Acid (SA), and arachidonic-induced platelet aggregation (Multiplate® analyzer). Residual platelet reactivity was measured by impedance change over 6 min and expressed as arbitrary units (U). The area under the concentration-time curves of ASA (AUCASA) and SA (AUCSA) from 4 h to 6 h were calculated and correlated with the corresponding platelet reactivity measure (U). Results: Platelet reactivity, AUCASA, AUCSA and AUCSA/AUCASA were highly variable among subjects. According to pre-set U cut-off values (28), 54.2% of patients were full responders, 8.3% partial responders and 37.5% poor responders. Antiplatelet effect of ASA correlated inversely with AUCASA and directly with AUCSA/AUCASA ratio (as a marker of ASA deacetylation rate). No thromboembolic or bleeding complications were recorded during follow-up. Conclusion: We posit that our results might be explained acknowledging that platelet cyclooxygenase-1 is more influential than intestinal and liver carboxylesterases in pre-systemic ASA deacetylation.
Pharmacodynamics; Pediatric patients; ASA
Padrini M, Spiezia L, De Rosa G, Simioni P, Milanesi O, Padrini R. Pharmacodynamics and Pharmacokinetics of Aspirin in Pediatric Patients. Ann Clin Pharmacol Ther. 2019; 2(1): 1006..