Physiologically-based pharmacokinetic modelling | Wikipedia audio article
Channel: wikipedia tts
Date: 03/05/2019

This is an audio version of the Wikipedia Article:
https://en.wikipedia.org/wiki/Physiologically_based_pharmacokinetic_modelling


00:02:15 1 History
00:03:18 2 Building a PBPK model
00:04:15 2.1 Basic transport equations
00:06:18 2.2 Modeling inputs
00:06:38 2.2.1 Ingestion
00:09:51 2.2.2 Skin depot
00:16:22 2.2.3 Intra-venous injection
00:16:37 2.2.4 Inhalation
00:16:51 2.3 Modelling metabolism
00:17:46 3 Uses of PBPK modeling
00:20:42 4 Limits and extensions of PBPK modeling



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SUMMARY
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Physiologically based pharmacokinetic (PBPK) modeling is a mathematical modeling 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 risk assessment 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, pharmacokinetic models. PBPK models may have purely predictive uses, but other uses, such as statistical inference, have been made possible by the development of Bayesian 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 multi-compartment models, with compartments corresponding to predefined organs or tissues, with interconnections corresponding to blood or lymph flows (more rarely to diffusions). A system of differential equations 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.