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Application of Permeability-limited Physiologically-based Pharmacokinetic Models: Part II—Prediction of P-glycoprotein Mediated Drug-drug Interactions with Digoxin

Digoxin is the recommended substrate for assessment of P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) in vivo. The overall aim of our study was to investigate the inhibitory potential of both verapamil and norverapamil on the P-gp-mediated efflux of digoxin in both gut and liver. Therefore, a physiologically-based pharmacokinetic (PBPK) model for verapamil and its primary metabolite … Continued

Application of Permeability-limited Physiologically-based Pharmacokinetic Models: Part I—Digoxin Pharmacokinetic Incorporating P-glycoprotein-mediated Efflux

A prerequisite for the prediction of the magnitude of P-glycoprotein (P-gp)-mediated drug-drug interactions between digoxin and P-gp inhibitors (e.g. verapamil and its metabolite norverapamil) or P-gp inducers (e.g. rifampicin) is a predictive pharmacokinetic model for digoxin itself. Thus, relevant in vitro metabolic, transporter and inhibitory data incorporated into permeability-limited models, such as the “advanced dissolution, … Continued

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