Physiologically based pharmacokinetics (PBPK)

  title={Physiologically based pharmacokinetics (PBPK)},
  author={Pascal Espié and Dominique Tytgat and Maria Laura Sargentini-Maier and Italo Poggesi and Jean Baptiste Watelet},
  journal={Drug Metabolism Reviews},
  pages={391 - 407}
Allometric scaling is widely used to predict human pharmacokinetic parameters from preclinical species, and many different approaches have been proposed over the years to improve its predictive performance. Nevertheless, prediction errors are commonly observed in the practical application of simple allometry, for example, in cases where the hepatic metabolic clearance is mainly determined by enzyme activities, which do not scale allometrically across species. Therefore, if good correlation was… 

Ethambutol disposition in humans: challenges and limitations of whole-body physiologically-based pharmacokinetic modelling in early drug development.

Physiologically Based Pharmacokinetic Models in the Prediction of Oral Drug Exposure Over the Entire Pediatric Age Range—Sotalol as a Model Drug

The two PBPK models evaluated in this study reflected properly the age-related pharmacokinetic changes and predicted adequately the oral sotalol exposure in children of different ages, except in neonates.

Physiologically Based Pharmacokinetic Modeling of Chemical Mixtures

This chapter is to give an overview of what PBPK modeling is and how it can be used in the context of mixture toxicology, and existing modeling approaches that are available in the literature are presented for mixtures of various complexities.

Prediction of Drug Clearance from Enzyme and Transporter Kinetics.

This chapter covers the use of conventional as well as recently developed methods to predict metabolic and transporter-mediated clearance along with the advantages and disadvantages of using these methods and the associated experimental considerations.

Physiologically Based Pharmacokinetic Modeling: Methodology, Applications, and Limitations with a Focus on Its Role in Pediatric Drug Development

PBPK models can be applied to investigate drug pharmacokinetics under different physiological and pathological conditions or in different age groups, to support decision-making during drug discovery, and to provide data that can save time and resources, especially in early drug development phases and in pediatric clinical trials.

Interspecies scaling in pharmacokinetics: a novel whole-body physiologically based modeling framework to discover drug biodistribution mechanisms in vivo.

It is shown how experimental dose-response data in rats for immunosuppressant cyclosporin are sufficient for predicting the biodistribution of this drug in pigs, monkeys, and humans, and the predicted drug concentrations extrapolated by interspecies scaling laws match well with the experimental measurements.

Physiologically-based pharmacokinetics in drug development and regulatory science.

Specific advances and contemporary challenges with respect to predicting the processes of drug clearance, distribution, and absorption are reviewed, together with the ability to anticipate the quantitative extent of PK-based drug-drug interactions and the impact of age, genetics, disease, and formulation.

Predicting drug–drug interactions: application of physiologically based pharmacokinetic models under a systems biology approach

The main purpose of this review is to discuss the application of IVIVE in conjunction with physiologically based pharmacokinetic modeling under a systems biology approach to characterize the potential DDIs in individual patients, including those who cannot be investigated in formal clinical trials for ethical reasons.

A compatibility evaluation between the physiologically based pharmacokinetic (PBPK) model and the compartmental PK model using the lumping method with real cases

The compatibility between PBPK and compartment models was confirmed by the lumping method, and the relationship of the calculated Vd/fu and the accuracy of AUC between the lumped model and compartment model confirmed their compatibility.




It is concluded that the generic PBPK model is potentially a powerful and cost-effective tool for predicting the mammalian pharmacokinetics of a wide range of organic compounds, from readily available in vitro inputs only.

Physiologically based pharmacokinetic (PBPK) modeling of disposition of epiroprim in humans.

Overall, using the TCM and the NAS for the parameterization of the distribution and clearance, respectively, the PBPK model gave the more accurate predictions of epiroprim's disposition in human.

Physiologically based pharmacokinetic modelling: a sound mechanistic basis is needed.

  • L. Aarons
  • Biology, Medicine
    British journal of clinical pharmacology
  • 2005
The idea is that pharmacokinetics accounts for some of the variability in the dose-response relationship, and in order to transform dose into concentration, a pharmacokinetic model is required, based on an analysis of concentration-time data and preferably incorporating relevant patient characteristics, allowing it to be used for individualized therapy.

Evaluation of a Generic Physiologically Based Pharmacokinetic Model for Lineshape Analysis

  • S. Peters
  • Biology, Chemistry
    Clinical pharmacokinetics
  • 2008
The validation of the generic PBPK model built in-house demonstrated that as long as the absorption profile of a compound is determined solely by solubility and paracellular or transcellular permeability, the P BPK simulations of oral profiles using optimized parameters from intravenous simulations provide reasonably good agreement with the observed profile.


The generic physiologically based pharmacokinetic model, as a means of integrating readily determined in vitro and/or in silico data, is potentially a powerful, cost-effective tool for predicting human xenobiotic kinetics in drug discovery and risk assessment.

Prediction of pharmacokinetics prior to in vivo studies. II. Generic physiologically based pharmacokinetic models of drug disposition.

The results indicate that most of the simulated concentration-time profiles of plasma and 10 tissues are in reasonable agreement with the corresponding experimental data determined in vivo (less than a factor of two), however, some more relevant deviations were observed for specific tissues.

Prediction of Hepatic Metabolic Clearance Based on Interspecies Allometric Scaling Techniques and In Vitro-In Vivo Correlations

In contrast to purely empirical approaches, the physiological approach to predicting clearance gives an opportunity to integrate some of these complexities and, therefore, should provide more confidence in the prediction of clearance in humans.

Prediction of Human Pharmacokinetics Using Physiologically Based Modeling: A Retrospective Analysis of 26 Clinically Tested Drugs

The physiologically based pharmacokinetics (PBPK) model, which combined methods Vd2 and CL2 yielded the most accurate predictions of in vivo terminal half-life (69% within 2-fold), demonstrates that PBPK models can lead to reasonable predictions of human pharmacokinetic predictions.

Development and Application of Physiologically Based Pharmacokinetic‐Modeling Tools to Support Drug Discovery

A generic disposition model based on tissue‐composition‐based distribution and directly scaled hepatic clearance is presented, which can be used in drug discovery to identify the critical PK issues of compound classes and to rationally guide the optimization path of the compounds toward a viable development candidate.

Evaluation of human pharmacokinetics, therapeutic dose and exposure predictions using marketed oral drugs.

For oral therapies, human PK parameters and clinical dose can be estimated from a consideration of data obtained from in vitro screens using human derived material and in vivo animal studies, and a good correlation between predicted and observed dose is suggested.