Ann Clin Pharmacol Ther | Volume 2, Issue 1 | Research Article | Open Access

Pharmacodynamics and Pharmacokinetics of Aspirin in Pediatric Patients

Maddalena Padrini¹, Luca Spiezia², Giovanni De Rosa³, Paolo Simioni², Ornella Milanesi¹ and Roberto Padrini^3*

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, Italy

^*Correspondance to: Roberto Padrini 

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Abstract

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 (AUC_ASA) and SA (AUC_SA) from 4 h to 6 h were calculated and correlated with the corresponding platelet reactivity measure (U). Results: Platelet reactivity, AUC_ASA, AUC_SA and AUC_SA/AUC_ASA 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 AUC_ASA and directly with AUC_SA/AUC_ASA 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.

Keywords:

Pharmacodynamics; Pediatric patients; ASA

Citation:

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..