Premium
In Silico Modeling of the Antiplatelet Pharmacodynamics of Low‐dose Aspirin in Health and Disease
Author(s) -
Giaretta A,
Rocca B,
Di Camillo B,
Toffolo GM,
Patrono C
Publication year - 2017
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.694
Subject(s) - aspirin , pharmacodynamics , platelet , medicine , pharmacology , in silico , dosing , essential thrombocythemia , pharmacokinetics , population , cyclooxygenase , physiologically based pharmacokinetic modelling , biology , biochemistry , gene , enzyme , environmental health
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 B 2 (sTXB 2 ), 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 sTXB 2 inhibition in healthy (accuracy = 10.4%), the reduced inhibition of sTXB 2 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.