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Pharmacokinetic models range from being entirely exploratory and empirical, to semi-mechanistic and ultimately complex physiologically based pharmacokinetic (PBPK) models. This choice is conditional on the modelling purpose as well as the amount and quality of the available data. The main advantage of PBPK models is that they can be used to extrapolate(More)
The utilisation of physiologically-based pharmacokinetic models for the analysis of population data is an approach with progressively increasing impact. However, as we move from empirical to complex mechanistic model structures, incorporation of stochastic variability in model parameters can be challenging due to the physiological constraints that may(More)
To investigate the effect of OATP1B1 genotype as a covariate on repaglinide pharmacokinetics and drug-drug interaction (DDIs) risk using a reduced physiologically-based pharmacokinetic (PBPK) model. Twenty nine mean plasma concentration-time profiles for SLCO1B1 c.521T>C were used to estimate hepatic uptake clearance (CLuptake) in different genotype groups(More)
To develop a population physiologically-based pharmacokinetic (PBPK) model for simvastatin (SV) and its active metabolite, simvastatin acid (SVA), that allows extrapolation and prediction of their concentration profiles in liver (efficacy) and muscle (toxicity). SV/SVA plasma concentrations (34 healthy volunteers) were simultaneously analysed with NONMEM(More)
In this work, we first describe the population variability in hepatic drug metabolism using cryopreserved hepatocytes from five different donors cultured in a perfused three-dimensional human liver microphysiological system, and then show how the resulting data can be integrated with a modeling and simulation framework to accomplish in vitro-in vivo(More)
Whole-body physiologically based pharmacokinetic (PBPK) models are increasingly used in drug development for their ability to predict drug concentrations in clinically relevant tissues and to extrapolate across species, experimental conditions and sub-populations. A whole-body PBPK model can be fitted to clinical data using a Bayesian population approach.(More)
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