Abstract
There have been efforts to develop physiologically based pharmacokinetic (PBPK) models for nanomaterials (NMs). Since NMs have quite different kinetic behaviors, the applicability of the approaches and techniques that are utilized in current PBPK models for NMs is warranted. Most PBPK models simulate a size-independent endocytosis from tissues or blood. In the lungs, dosimetry and the air-liquid interface (ALI) models have sometimes been used to estimate NM deposition and translocation into the circulatory system. In the gastrointestinal (GI) tract, kinetics data are needed for mechanistic understanding of NM behavior as well as their absorption through GI mucus and their subsequent hepatobiliary excretion into feces. Following absorption, permeability (Pt) and partition coefficients (PCs) are needed to simulate partitioning from the circulatory system into various organs. Furthermore, mechanistic modelling of organ- and species-specific NM corona formation is in its infancy. More recently, some PBPK models have included the mononuclear phagocyte system (MPS). Most notably, dissolution, a key elimination process for NMs, is only empirically added in some PBPK models. Nevertheless, despite the many challenges still present, there have been great advances in the development and application of PBPK models for hazard assessment and risk assessment of NMs.
Highlights
Physiologically-based pharmacokinetic (PBPK) modelling is a computational approach that simulates the absorption, distribution, metabolism and elimination (ADME) of chemical substances in the bodies of organisms
In PBPK modelling, hepatobiliary clearance is presented from the extravascular compartment of liver to a fecal compartment, representing the transport of NMs from liver to gut through bile [13], as shown in Equation (11) (which is similar to Equation (6) above): dABiliary excretion dt
While most PBPK models have been used to estimate the biodistribution of NMs, Laomettachit et al [20] examined the toxicity of TiO2 NPs on human liver in a two-step approach that combined a PBPK model and a cell-response model, where the latter model was used to predict liver cell viability and cell death resulting from accumulated TiO2 NPs
Summary
Physiologically-based pharmacokinetic (PBPK) modelling is a computational approach that simulates the absorption, distribution, metabolism and elimination (ADME) of chemical substances in the bodies of organisms. Development of PBPK models requires species-specific physiological and anatomical data as well as substance-specific pharmacokinetic data and partition coefficients of the compound in various tissues [4]. Using these parameters, PBPK models have been developed for many conventional substances including organic compounds and other inorganic substances. As there are major differences between the ADME behaviors of nanomaterials (NMs) and those of conventional chemical compounds, some additional factors should be considered in the development of PBPK models for NMs [5].
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