Quantitative Prediction of Drug–Drug Interactions Involving Inhibitory Metabolites in Drug Development: How Can Physiologically Based Pharmacokinetic Modeling Help?. (19th September 2016)

• Record Type: Journal Article
• Authors: Templeton, IE; Chen, Y; Mao, J; Lin, J; Yu, H; Peters, S; Shebley, M; Varma, MV
• Is Part Of: CPT: pharmacometrics & systems pharmacology. Volume 5:Number 10(2016:Oct.)
• Page Start: 505
• Page End: 515
• Publication Date: 2016-09-19
• Subjects: Pharmacokinetics -- Periodicals; Pharmacology -- Periodicals; Pharmacokinetics; Periodicals; 615.05
• DOI: 10.1002/psp4.12110
• Languages: English
• ISSNs: 2163-8306

Abstract

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.