Physiologically based pharmacokinetics (PBPK)

Physiologically based pharmacokinetics is a more mechanistic and physiologically approved way to describe drug dynamics in whole organisms as compared with classical compartmental approaches. This approach takes into account the physiological characteristics of the organism: size and composition of organs, blood flow rates, and so on, as well as the physicochemical properties of the compound. Since the approach is able to combine different types of data and information, typical PBPK models are more flexible in data integration and more powerful in predictions. Well-verified PBPK models can simulate or even predict the dynamics of drugs not only in the blood but also in particular organs or organ parts. For example, there are PBPK methods predicting drug clearance by liver enzymes or through the urine in humans on the basis of preclinical and in vitro data, which is impossible to predict by compartmental PK/PD modeling. By combining the PBPK approach with the statistical population approach, it is possible to perform “virtual clinical trials,” i.e. predict clinical trial results to correct the design or sample size.

Method application:

  • Choice of optimal regimens and doses for humans on the basis of preclinical data (advanced allometric scaling);
  • Prediction of drug candidate pharmacokinetics on the basis of physicochemical properties at the initial stages of drug development;
  • Prediction of compound concentrations in tissues (organs) on the basis of plasma concentration;
  • Performing of “virtual clinical trials”;
  • Prediction of optimal physicochemical properties of compounds to obtain optimal pharmacokinetics;
  • Help in decision making to determine the optimal route of administration or treatment: oral, inhalation, intravenous, etc.;
  • Prognosis of pharmacokinetics for special populations: renal, liver failure, children, etc.;
  • Prediction of the optimal individual dose (personalized medicine) on the basis of individual physiological characteristics.