| Popis: |
Physiologically based pharmacokinetic (PBPK) models differ from classical PK models in that they include specific compartments for tissues involved in exposure, toxicity, biotransforma‐ tion and clearance processes connected by blood flow (Figure 1). Compartments and blood flows are described using physiologically meaningful parameters, which allows for interspe‐ cies extrapolation by altering the physiological parameters appropriately [1]. A key benefit to PBPK models is that factors influencing the absorption, distribution, metabolism, and elimi‐ nation of a compound can be incorporated into a PBPK model in a mechanistic, meaningful way, if a mechanism is understood and sufficient data are available. This mechanistic aspect is supported by physiological parameters influencing absorption (e.g., pH values and transit times through various sections of the GI tract), distribution (e.g., tissue volumes and compo‐ sition), metabolism (e.g., expression levels of various hepatic enzymes and transporters involved with metabolic elimination), and elimination (e.g., glomerular filtration rate and expression levels of transporters in the kidneys involved with renal elimination), which can be explicitly incorporated in the PBPK model. |
