Quantitative Systems Pharmacology Model of Thrombopoiesis and Platelet Life-cycle, and Its Application to Thrombocytopenia Based on Chronic Liver Disease

Overview

Journal CPT Pharmacometrics Syst Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2021 Apr 2

PMID 33797208

Citations 1

Authors

Ryosuke Shimizu

Takayuki Katsube

Toshihiro Wajima

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Recent applications of quantitative systems pharmacology and machine learning models across diseases.

Aghamiri S, Amin R, Helikar T J Pharmacokinet Pharmacodyn. 2021; 49(1):19-37.

PMID: 34671863 PMC: 8528185. DOI: 10.1007/s10928-021-09790-9.

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