In Silico Modeling of the Antiplatelet Pharmacodynamics of Low-dose Aspirin in Health and Disease

Bianca Rocca, Carlo Patrono, A. Giaretta, B. Di Camillo, G. M. Toffolo

Risultato della ricerca: Contributo in rivistaArticolo in rivista

13 Citazioni (Scopus)

Abstract

The influence of platelet turnover on cyclooxygenase (COX-1) inhibition by low-dose aspirin remains largely uncharacterized due to limited feasibility of studying aspirin pharmacodynamics in bone marrow precursors. We developed an in silico compartmental model describing the aspirin effects on COX-1 activity in a population of megakaryocytes (MK) and in peripheral platelets. Model parameters were inferred from the literature and calibrated using measurements of serum thromboxane B2 (sTXB2), as proxy of COX-1 activity in peripheral platelets, in 17 healthy subjects and 24 patients with essential thrombocythemia (ET). The model reproduced well the average time-course of sTXB2 inhibition in healthy (accuracy = 10.4%), the reduced inhibition of sTXB2 observed in ET, and the effect of different dosing regimens. In conclusion, the in silico model accurately describes COX-1 inactivation by low-dose aspirin in MK and platelets in different clinical settings, and might help personalize aspirin regimens in conditions of altered megakaryopoiesis.
Lingua originaleEnglish
pagine (da-a)823-831-831
RivistaCLINICAL PHARMACOLOGY & THERAPEUTICS
Volume102
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • Pharmacology
  • antiplatelet
  • clinical pharmacology
  • in silico modelling

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