Predicting variations in drug clearance in obese patients using modeling and simulation

PBPK modeling and simulation in virtual obese patient populations can identify potential changes in drug disposition that may impact upon drug safety and efficacy in this patient group and help guide dosing decisions

Many physiological changes are associated with obesity and can potentially impact on pharmacokinetics. This can require adjustments to be made to the standard doses for normal weight patients in order to ensure safety and efficacy of drug therapy. Physiologically-based pharmacokinetic (PBPK) models incorporate the known, relevant demographic, anatomical and physiological variables associated with obesity in order to predict drug clearance with reasonable accuracy in obese and morbidly obese subjects.

Certara® scientists applied a ‘systems biology’ approach to identify the likelihood of observing variations in drug clearance in obesity and morbid obesity for a set of compounds for which clinical data, as well as the necessary in vitro information, were available. First, obese and morbidly obese virtual populations were built through collation of data on a variety of parameters including: body surface area, cardiac output, liver and kidney volumes, organ blood flow for the liver, kidney and GI tract, enzyme activity for specific CYPs and plasma protein binding.

 

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