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Graphic representation of a physiologically based whole body model. Here, it is dissected into seven tissue/organ compartments: brain, lungs and heart, pancreas, liver, gut, kidney and adipose/muscle tissue.
Blood flows, Q, and concentration, [X], of a substance of interest are depicted. Physiologically based pharmacokinetic (PBPK) modeling is a technique for predicting the absorption, distribution, metabolism and excretion (ADME) of synthetic or natural chemical substances in humans and other animal species. PBPK modeling is used in pharmaceutical research and drug development, and in health for cosmetics or general chemicals. PBPK models strive to be mechanistic by mathematically transcribing anatomical, physiological, physical, and chemical descriptions of the phenomena involved in the complex ADME processes. A large degree of residual simplification and empiricism is still present in those models, but they have an extended domain of applicability compared to that of classical, empirical function based, models. PBPK models may have purely predictive uses, but other uses, such as statistical inference, have been made possible by the development of statistical tools able to deal with complex models. That is true for both toxicity risk assessment and therapeutic drug development.
PBPK models try to rely a priori on the anatomical and physiological structure of the body, and to a certain extent, on biochemistry. They are usually, with compartments corresponding to predefined organs or tissues, with interconnections corresponding to blood or lymph flows (more rarely to diffusions). A system of for concentration or quantity of substance on each compartment can be written, and its parameters represent blood flows, pulmonary ventilation rate, organ volumes etc., for which information is available in scientific publications.
Indeed, the description they make of the body is simplified and a balance needs to be struck between complexity and simplicity. Besides the advantage of allowing the recruitment of a priori information about parameter values, these models also facilitate inter-species transpositions or extrapolation from one mode of administration to another ( e.g., inhalation to oral). An example of a 7-compartment PBPK model, suitable to describe the fate of many solvents in the mammalian body, is given in the Figure on the right. Simulated drug plasma concentration over time curves following IV infusion and multiple oral doses. The drug has an of 4 hours, and an apparent of 10 liters. PBPK models are compartmental models like many others, but they have a few advantages over so-called 'classical' pharmacokinetic models, which are less grounded in physiology. Windows 2008 R2 Sp2 64 Bit Torrent. PBPK models can first be used to abstract and eventually reconcile disparate data (from physicochemical or biochemical experiments, or pharmacological or toxicological experiments, etc.) They give also access to internal body concentrations of chemicals or their metabolites, and in particular at the site of their effects, be it therapeutic or toxic.
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• Ramsey J, Andersen M (1984). 'A physiologically based description of the inhalation pharmacokinetics of styrene in rats and humans'.. 73: 159–175.. (2005) Physiologically Based Pharmacokinetic Modeling: Science and Applications, Wiley-Interscience.
• Peters S.A (2012) Physiologically-Based Pharmacokinetic (PBPK) Modeling and Simulations, Wiley. Forums [ ] • is a website on mathematical models in ecotoxicology.
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