Existing non-Dinmotion PBPK models provide simulation in static conditions. This is quite far from reality – a living organism would rarely remain immobile; variety of external and internal environmental parameters may change and certain level of models’ adaptability is required.
Dinmotion PBPK models allow simulation under the impact of:
1) dynamically changing model’s external environment parameters such as:
– air pressure (or, in other words, pressure of breathing gas mixture);
– partial pressure of oxygen;
– partial pressure of carbon dioxide;
– partial pressure of any inert gas etc.
2) dynamically changing model’s internal environment parameters such as:
– physical load (changing consumption of oxygen and level of production of carbon dioxide);
– hemoglobin and/or myoglobin concentration;
– lungs ventilation/ volume/frequency;
– other parameters that may change because of pharmacological correction of pathologic states and have impact on blood dynamics as well as on diffusion of respiratory gases.
3) dynamically changing temperature regimes.
Some parameters may change as concentration of compounds grows or goes down. The possible impact on drug dynamics parameters is identified and evaluated and corresponding trajectories are built, metrics introduced and calculations provided.
Can I ask how you control blood circulation?
We are using special solutions based on mathematical optimal control theory. You can use as a reference our paper “Simulation of drug dynamic parameters and optimization models of the functional respiratory system in pharmacokinetic studies.” published in Nonlinear Analysis: Theory, Methods & Applications
Looks quite interesting… Is it possible to simulate the treatment of traumatic brain injury with hyperoxia?
yes, we would need to simulate pre-defined regimes of lungs ventilation with appropriate functions or introduce a mechanism of the search of optimal regimes
Can I ask if Physiologically Based Pharmacokinetic (PBPK) simulation models are used for pharmacological correction of body systems to rehabilitate them after high physical load? If not, are you planning to do it in the future? Is it possible to use PBPK models for that and to what extent?
They are not widely used so far because the task of creation of such models is extremely complex. To receive valid simulation results, traditional Physiologically Based Pharmacokinetic (PBPK) models are not sufficient; frankly, they are very far from that. The task requires a combination of Dinmotion PBPK models with models of other human body systems such as models of Erythropoiesis, a model of hypometabolism, models of energy exchange and possibly others. Such complex models require intricate mathematical mechanisms of control to be implemented to satisfy simulation requirements. Dinmotion built and justified the complex integrated model using highly sophisticated mathematical approach which included methods of non-linear differential equations, methods of least squares, Game theory, Optimal Control theory, methods of numerical calculations, etc. This model simulates revitalization of oxygen regimes of a human body by several methods of an antihypoxic drug administration – intravenous injection, intramuscular injection or inhalation. You are always welcome to contact us if you need further assistance or if you need more information