Assessing Drug-Smoking Interactions Using PBPK Modeling

Theresa Cain

The prevalence of cigarette smoking remains high globally despite abundant evidence showing that it isn’t good for your health. But, did you know that smoking can affect the metabolism of other drugs and even cause serious drug interactions? In this blog post, I’ll discuss the mechanisms by which smoking can impact pharmacokinetics, how physiologically-based pharmacokinetic […]

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Topics: Model-based Drug Development, PBPK Modeling and Simulation

Applications of linking PBPK and PD models to predict the impact of genotypic variability, formulation differences, differences in target binding capacity and target site drug concentrations on drug responses and variability.

This study aimed to demonstrate the added value of integrating prior in vitro data and knowledge-rich physiologically based pharmacokinetic (PBPK) models with pharmacodynamics (PDs) models. Four distinct applications that were developed and tested are presented here. PBPK models were developed for metoprolol using different CYP2D6 genotypes based on in vitro data. Application of the models for prediction of phenotypic differences in the pharmacokinetics (PKs) and PD compared […]

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Deciding on Success Criteria for Predictability of Pharmacokinetic Parameters from In Vitro Studies: An Analysis Based on In Vivo Observations

Prediction accuracy of pharmacokinetic parameters is often assessed using prediction fold error, i.e., being within 2-, 3-, or n-fold of observed values. However, published studies disagree on which fold error represents an accurate prediction. In addition, “observed data” from only one clinical study are often used as the gold standard for in vitro to in vivo extrapolation (IVIVE) studies, despite data being subject to significant […]

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