Pharmacokinetic-pharmacodynamic model physiological parameters

The Optimization Module aids in the optimization (fitting) of a wide variety of model parameters including physiological, pharmacokinetic, pharmacodynamic, and formulation variables. 

Table 1 Biological parameters required for pyrethroid insecticide physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models ...

What are called physiologically based pharmacokinetic (PBPK) and pharmacodynamic (PBPD) models are more mechanistically complex and often include more compartments, more parameters, and more detailed expressions of rates and fluxes and contain more mechanistic representation. This type of model is reviewed in more detail in Section 22.5. Here, we merely classify such models and note several characteristics. PBPK models have more parameters, are more mechanistic, can exploit a wider range of data, often represent the whole body, and can be used both to describe and interpolate as well as to predict and extrapolate. Complexity of such models ranges from moderate to high. They typically contain 10 or more compartments, and can range to hundreds. The increase in the number of flux relationships between compartments and the related parameters is often more than proportional to compartment count. 

Using human physiology and in vitro data and clinically relevant input parameters (i.e., metabolic stability in human hepatocytes and microsomes as well as prothrombin time measured in various batches of human plasma) the model was extended to human. This human PK/PD model was then used to investigate the impact of the various physicochemical, pharmacokinetic and pharmacodynamic properties on the anticoagulant profile (i.e., prothrombin time) expected in man. 

Exposures of newborns to PAHs depend on pharmacokinetic processes operating in the mother, and transfer through breast milk. Since it is difficult to characterize these pathways in humans, physiologically based pharmacokinetic (PBPK) and pharmacodynamic (PD) models need to be developed using appropriate animal models, and incorporating key parameters such as dose, exposure duration, and developmental stage (Dorman et al, 2001). Thus, development of PBPK and PBPD models for PAHs is an immediate need that will help in not only characterizing the dose-response relationship, but also extrapolation of results from animal studies to humans. 

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