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In Silico Modeling of the Antiplatelet Pharmacodynamics of Low-dose Aspirin in Health and Disease.
- Source :
- Clinical Pharmacology & Therapeutics; Nov2017, Vol. 102 Issue 5, p823-831, 9p
- Publication Year :
- 2017
-
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 B<subscript>2</subscript> (sTXB<subscript>2</subscript>), 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<subscript>2</subscript> inhibition in healthy (accuracy = 10.4%), the reduced inhibition of sTXB<subscript>2</subscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00099236
- Volume :
- 102
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Clinical Pharmacology & Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 125581370
- Full Text :
- https://doi.org/10.1002/cpt.694