Biomedical Engineering Reference
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Fig. 12.3 Schematic representation of a hypothetical QSP model. Drug concentration-time
profiles in the plasma and tissues are described by a whole-body PBPK model. Drug distribution
to tumor is described in greater detail to delineate concentrations in tumor cells, where the drug
target is, rather than total tumor concentration. The model incorporates key molecular
intermediates in tumor cells, rather than the entire network, which may be useful in understanding
temporal delays in downstream signaling events
compartments in PBPK models represent tissues, organs, or groups of tissues that
carry anatomic and physiologic meaning. PBPK models are ODE-based models
that utilize a large body of physiologic and physiochemical data, allowing for better
extrapolation between doses, routes of administration, and species. Additionally,
the mechanistic nature of PBPK models allows for a priori prediction of plasma and
tissue data. The fundamental objective of PBPK modeling is to identify the princi-
ple organs or tissues involved in the disposition of the compound of interest and to
correlate absorption, distribution, and elimination within and among these organs
and tissues in an integrated and biologically plausible manner [ 9 , 43 , 79 ].
A schematic representation of a QSP model to describe multi-organ and multi-
cellular distribution of a compound is shown in Fig. 12.3 . The QSP model
incorporates a whole-body PBPK model with a multicellular tumor compartment.
Mass-balance differential equations are developed for each individual compartment
and are then simultaneously solved. Since equations are developed for each com-
partment, different levels of complexity can be integrated into specific
compartments. For instance, as illustrated in Fig. 12.3 , if we decide that the
tumor is not a single well-stirred compartment, but made up of tumor cells, stromal
cells, and extravascular extracellular space, we can write the mathematical term to
describe it. We can establish the distribution of drug (or any other endogenous or
exogenous molecule, protein, or antibody) to be perfusion or permeability limited,
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