Quantitative Prediction of Drug–Drug Interactions Involving Inhibitory Metabolites in Drug Development: How Can Physiologically Based Pharmacokinetic Modeling Help?

This subteam under the Drug Metabolism Leadership Group (Innovation and Quality Consortium) investigated the quantitative role of circulating inhibitory metabolites in drug–drug interactions using physiologically based pharmacokinetic (PBPK) modeling. Three drugs with major circulating inhibitory me...

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Detalles Bibliográficos
Autores principales: Templeton, IE, Chen, Y, Mao, J, Lin, J, Yu, H, Peters, S, Shebley, M, Varma, MV
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Tutorial
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080647/
https://www.ncbi.nlm.nih.gov/pubmed/27642087
http://dx.doi.org/10.1002/psp4.12110
Descripción
Sumario:This subteam under the Drug Metabolism Leadership Group (Innovation and Quality Consortium) investigated the quantitative role of circulating inhibitory metabolites in drug–drug interactions using physiologically based pharmacokinetic (PBPK) modeling. Three drugs with major circulating inhibitory metabolites (amiodarone, gemfibrozil, and sertraline) were systematically evaluated in addition to the literature review of recent examples. The application of PBPK modeling in drug interactions by inhibitory parent–metabolite pairs is described and guidance on strategic application is provided.

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