Clinical Pharmacology & Pharmacokinetics, Shionogi & Co., Ltd, Osaka, Japan.
CPT Pharmacometrics Syst Pharmacol. 2021 May;10(5):489-499. doi: 10.1002/psp4.12623. Epub 2021 May 3.
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.
血小板由造血干细胞通过骨髓中的巨核细胞产生，在止血中发挥着关键作用。本研究旨在通过定量系统药理学建模方法建立一种新的血小板模型，该模型可以描述血小板相关疾病和药物干预中血小板计数谱的变化。所提出的血小板模型由 44 个组件组成。该模型应用于促血小板生成素受体激动剂鲁索替尼的促血小板生成作用。它可以很好地描述健康受试者和慢性肝病伴血小板减少症患者给予鲁索替尼后的血小板计数谱。该模型对于了解血小板相关疾病的疾病进展，如血小板减少症，以及预测与血小板相关的各种疾病情况下的血小板计数谱和药物开发中的药物给药情况，应该是有用的。
