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Updated: Mar 14, 2026

Diagonal Method to Measure Synergy Among Any Number of Drugs
Published on: June 21, 2018
Quantitative Prediction of Drug-Drug Interactions Involving Inhibitory Metabolites in Drug Development: How Can
I E Templeton1, Y Chen2, J Mao2
1Genentech, South San Francisco, California, USA. templeton.ian@gene.com.
Abstract:
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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