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Pharmacometrics and systems pharmacology for metabolic bone diseases
Author(s) -
Riggs Matthew M.,
Cremers Serge
Publication year - 2019
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13881
Subject(s) - medicine , clinical pharmacology , teriparatide , denosumab , drug , osteoporosis , pharmacology , drug development , sclerostin , intensive care medicine , bioinformatics , biology , bone mineral , wnt signaling pathway , biochemistry , gene
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).