Quantitative systems pharmacology model of thrombopoiesis and platelet life-cycle, and its application to thrombocytopenia based on chronic liver disease.

Ryosuke Shimizu, Takayuki Katsube, Toshihiro Wajima

CPT: pharmacometrics & systems pharmacology 2021 May

filter terms:

Platelets are produced by hematopoietic stem cells via megakaryocytes in the bone marrow and play a critical role in hemostasis. The aim of this study was to develop a new platelet model based on the thrombopoiesis and platelet life-cycle by a quantitative systems pharmacology modeling approach, which could describe changes in platelet count profiles in platelet-related diseases and drug intervention. The proposed platelet model consists of 44 components. The model was applied to thrombopoiesis of a thrombopoietin receptor agonist, lusutrombopag. It could well describe the observed platelet count profiles after administration of lusutrombopag for both healthy subjects and patients with chronic liver disease and thrombocytopenia. This model should be useful for understanding the disease progression of platelet-related conditions, such as thrombocytopenia and for predicting platelet count profiles in various disease situations related to platelets and drug administration in drug development. © 2021 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

Citation

Ryosuke Shimizu, Takayuki Katsube, Toshihiro Wajima. Quantitative systems pharmacology model of thrombopoiesis and platelet life-cycle, and its application to thrombocytopenia based on chronic liver disease. CPT: pharmacometrics & systems pharmacology. 2021 May;10(5):489-499