Authors: Piet van der Graaf
Managing Immunogenicity Using Quantitative Systems Pharmacology
Biologic drug development is a rapidly evolving sector in the biopharmaceutical industry. Immunogenicity is an inherent challenge with this complex class of drugs. A quantitative systems pharmacology approach can be used to predict and better manage immunogenicity, and as a tool to guide clinical and regulatory decision-making in biologics drug development.
Read MoreA Parent-metabolite Pharmacokinetic Model of Paracetamol in Zebrafish
Quantifying the Growth Hormone Lowering Effect of BIM23B065 After a GH Stimulation Test
Accuracy of Plasma Clearance Scaling from Adults to Children Using Pathway-specific Covariate Models: A Systematic Investigation Using a Physiologically-based Pharmacokinetic Workflow
Pharmacokinetics and Pharmacodynamics of the Novel Somatostatin-dopamine Chimeric Compound BIM23B065 and Its Metabolite During a Growth Hormone Stimulation Test
A Six-stage Workflow for Robust Application of Systems Pharmacology
Quantitative and systems pharmacology (QSP) is increasingly being applied in pharmaceutical research and development. One factor critical to the ultimate success of QSP is the establishment of commonly accepted language, technical criteria, and workflows. We propose an integrated workflow that bridges conceptual objectives with underlying technical detail to support the execution, communication, and evaluation of […]
Read MoreQuantitative Systems Pharmacology Brings Value to Drug Development
Quantitative systems pharmacology (QSP) sits at the interface between pharmacometric modeling and simulation, and systems biology. It uses mathematics to describe biological processes. While pharmacokinetics describes what the body does to the drug, pharmacodynamics quantifies what the drug does to the body; the pharmacological response. QSP is a mechanistic modeling approach and an emerging technology, which mathematically integrates pharmacokinetics, pharmacological response and disease progress/modulation.
Read MoreThe Rise of Systems Pharmacology in Drug Discovery and Development
A Systems Pharmacology Perspective on the Clinical Development of Fatty Acid Amide Hydrolase Inhibitors for Pain
The level of the endocannabinoid anandamide is controlled by fatty acid amide hydrolase (FAAH). In 2011, PF-04457845, an irreversible inhibitor of FAAH, was progressed to phase II clinical trials for osteoarthritic pain. This article discusses a prospective, integrated systems pharmacology model evaluation of FAAH as a target for pain in humans, using physiologically based pharmacokinetic […]
Read MoreModel-based Drug Development: A Rational Approach to Efficiently Accelerate Drug Development
The pharmaceutical industry continues to face significant challenges. Very few compounds that enter development reach the marketplace, and the investment required for each success can surpass $1.8 billion. Despite attempts to improve efficiency and increase productivity, total investment continues to rise whereas the output of new medicines declines. With costs increasing exponentially through each development […]
Read MoreSystems Pharmacology of the Nerve Growth Factor Pathway: Use of a Systems Biology Model for the Identification of Key Drug Targets Using Sensitivity Analysis and the Integration of Physiology and Pharmacology
The nerve growth factor (NGF) pathway is of great interest as a potential source of drug targets, for example in the management of certain types of pain. However, selecting targets from this pathway either by intuition or by non-contextual measures is likely to be challenging. An alternative approach is to construct a mathematical model of […]
Read MoreSystems Pharmacology for Drug Discovery and Development: Paradigm Shift or Flash in the Pan?
Systems pharmacology is an emerging approach that sets out to use quantitative concepts rooted in the synergy between modeling and simulation on one hand and large-scale data collection and analysis on the other to investigate biological systems and design therapeutic interventions. Interest in this field has recently increased substantially, but so have perceived challenges and […]
Read MoreReducing Systems Biology to Practice in Pharmaceutical Company Research: Selected Case Studies
Reviews of the productivity of the pharmaceutical industry have concluded that the current business model is unsustainable. Various remedies for this have been proposed, however, arguably these do not directly address the fundamental issue; namely, that it is the knowledge required to enable good decisions in the process of delivering a drug that is largely […]
Read MoreSystems Pharmacology: Bridging Systems Biology and Pharmacokinetics/Pharmacodynamics (PK/PD) in Drug Discovery and Development
Mechanistic PKPD models are now advocated not only by academic and industrial researchers, but also by regulators. A recent development in this area is based on the growing realisation that innovation could be dramatically catalysed by creating synergy at the interface between Systems Biology and PKPD, two disciplines which until now have largely existed in […]
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