Physiologically based pharmacokinetic model

We are pleased to announce that our group's manuscript “Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues” has recently been published.

DOI: doi.org/10.1371/journal.pone.0249594.

Our group has developed a physiologically based metformin pharmacokinetic (PBPK) model based on human physiological parameters (blood flow, tissue volume, and others), data from preclinical species (mice) and in vitro data to predict the dynamics of metformin distribution in humans. Figure 1 provides a schematic representation of the developed model.

Figure 1: Schematic representation of a physiologically based pharmacokinetic model for metformin in mice and humans.


PBPK modelling and simulation is a useful tool to answer several questions throughout the process of drug development and its use in clinical practice. Thus it becomes a very popular technique that allows researchers to overcome practical limitations for clinical trials on special populations (drug-drug interactions or predicting the effects of age, genetics, or disease on pharmacokinetics). PBPK modelling, being in its early development, is a unique modelling tool of active substances as it can be applied to in-vitro and in-vivo translation and further be transferred from preclinical species to humans. PBPK modelling techniques can be utilized to (1) increase drug therapy efficiency, (2) reduce the need for animal studies, (3) sometimes replace clinical trials through the development phase of an active entity and (4) to increase understanding of pharmacokinetics. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate pharmacokinetics parameters and plasma concentration-time profiles but also to gain mechanistic insight into compound properties.

Moreover, PBPK is well established in the pharmaceutical industry and is accepted by regulatory agencies for the prediction of drug-drug interactions (1).



References:

  1. Rowland M, Peck C, Tucker G. Physiologically-based pharmacokinetics in drug development and regulatory science. Annu Rev Pharmacol Toxicol. 2011;51:45–73. doi: 10.1146/annurevpharmtox-010510-100540.