A workflow for resolving model internal consistency in use-reuse settings (aka repairing unstable models)

On the whole, model building for data analysis is a well-defined process with relatively few issues relating to a model’s internal consistency. The concept of model internal consistency is defined as a property of the model that is in some way inconsistent within itself rather than an inconsistency resulting from the interaction of the model […]

On mass balance and the use-reuse of the rate constant matrix in pharmacokinetics

Introduction Assurance of mass balance is a critical part of pharmacometric model formulation (i.e. model creation and coding).  In many cases, for simple mamillary compartmental models this can be assessed informally.  However, in more complicated models (e.g. physiologically based models) the proof of mass balance can be more complicated.  A method to evaluate mass balance […]

Issues with virtual populations when applied to nonlinear QSP models

Introduction Quantitative systems pharmacology (QSP) models describe the clinical pharmacological properties of a drug.  They are typically described as systems of linear mass-balance and nonlinear mass-action of drugs.  One of the purposes of QSP models is to simulate potential outcomes from virtual clinical trials. This approach is predicated on generating virtual populations of patients (a […]

PAGANZ Workshop: CellML and OpenCOR

Over the past 10 year quantitative systems pharmacology has become an integral part of pharmacometrics.  While the models and methods used in a QSP framework are novel to pharmacometricians they have been well established in the disciplines of systems biology and bioengineering.  Software (e.g. CellML, SBML, …) for specifying models and enabling simulations from models […]

An approach to evaluating mass and energy balance of pharmacokinetic systems using bond graph theory

Introduction: Quantitative systems pharmacology models are used in PKPD and pharmacometrics to describe the effects of drugs as modulators of system behaviour.  In most cases the systems that are described in these models can be constructed of modular units that can be assembled en-masse to create the overall system.  An example of a modular component […]

Development and application of a pharmacokinetic model for the glycation of albumin

Background Glycated haemoglobin, HbA1c, is used commonly as a marker for glycaemic control. In patients with chronic kidney disease (CKD) red blood cells (RBCs) are removed faster from the circulation, giving less time for glycation of haemoglobin to occur [1]. Thus, HbA1c concentrations are falsely lowered in these patients. Glycated albumin (GA) has been suggested […]

Evaluation of an optimal design for examining melphalan pharmacokinetics in patients with multiple myeloma

Background: The optimal design of population pharmacokinetics allows parameter estimation with minimum variance and reduced cost by identifying (1) the minimum number of blood samples required from each subject, (2) the optimal blood sampling times and (3) the minimum number of subjects required. Aim: To evaluate the results of an optimal design experiment that was […]