QSP Model Simplification Using Machine Learning with an Application to Heparin Dose-Response in Children

Introduction The coagulation network model is used to describe the relationship between an anticoagulant, or pro-coagulant, and a clotting test outcome [1]. The system consists of an in-vivo (62 ODEs and 184 parameters) and in-vitro (62 ODEs and 182 parameters) modules. These two modules are linked by a discontinuous interface with the whole function not being […]

Quantifying the Dose-Response of Unfractionated Heparin Using a System Pharmacology Model of Coagulation

Introduction: Unfractionated heparin (UFH) is commonly used in the treatment and prevention of a variety of thromboembolic disorders. Its short duration of action and reversibility of its effect with the use of protamine sulphate make it the agent of choice in acute settings such as cardiac surgery. However, optimal dosing of UFH remains challenging partly due […]