Pharmacometrics and systems pharmacology for metabolic bone diseases.

Abstract

Mathematical modelling and simulation (M&S) of drug concentrations, pharmacologic effects and the (patho)physiologic systems within which they interact can be powerful tools for the preclinical, translational and clinical development of drugs. Indeed, the Prescription Drug User Fee Act (PDUFA VI), incorporated as part of the FDA Reauthorization Act of 2017 (FDARA), highlights the goal of advancing model-informed drug development (MIDD). MIDD can benefit development across many drug classes, including for metabolic bone diseases such as osteoporosis, cancer-related and numerous rare metabolic bone diseases; conditions characterized by significant morbidity and mortality. A drought looms in terms of the availability of new drugs to better treat these devastating diseases. This review provides an overview of several M&S approaches ranging from simple pharmacokinetic to integrated pharmacometric and systems pharmacology modelling. Examples are included to illustrate the use of these approaches during the development of several drugs for metabolic bone diseases such as bisphosphonates, denosumab, teriparatide and sclerostin inhibitors (romosozumab and blosozumab).

• Authors: Matthew M Riggs, Serge Cremers
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 85 Issue 6 Pg. 1136-1146 (06 2019) ISSN: 1365-2125 [Electronic] England
• PMID: 30690761 (Publication Type: Journal Article, Review)
• Copyright: © 2019 The British Pharmacological Society.

Chemical References

• Bone Density Conservation Agents

Topics

• Animals
• Bone Density Conservation Agents (adverse effects, pharmacokinetics, therapeutic use)
• Bone Diseases, Metabolic (drug therapy, physiopathology)
• Bone Remodeling (drug effects)
• Computer Simulation
• Drug Development (methods)
• Drug Monitoring
• Humans
• Models, Biological
• Patient Safety
• Risk Assessment
• Systems Biology