Physiologically Based Pharmacokinetic (<scp>PBPK</scp>) Modeling: Usefulness and Applications

Maeng, Han‐Joo; Chow, Edwin; Fan, Jianghong; Pang, K. Sandy

doi:10.1002/9780470921920.edm036

Cited by 3 publications

(2 citation statements)

References 191 publications

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“…Perhaps most importantly, the pharmacokinetics of delivering chemical agents to the in vivo site of the enzyme is inherently based on stepwise transport kinetics, which is conceptually identical to stepwise chemical kinetics. [5] Accounting for multiple steps of dynamic kinetic processes can be overwhelming, and often requires additional measurements or assumptions to simplify the analysis. In addition, other in vivo conditions besides enzyme activity can influence a chemical assay, so that care must be taken to ensure that the assay is specifically reporting on enzyme activity.…”

Section: Introductionmentioning

confidence: 99%

Detecting Enzyme Activities with Exogenous MRI Contrast Agents

Hingorani¹,

Yoo²,

Bernstein³

et al. 2014

Chemistry A European J

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This review focuses on exogenous MRI contrast agents that are responsive to enzyme activity. Enzymes can catalyze a change in water access, rotational tumbling time, the proximity of a 19F-labeled ligand, the aggregation state, the proton chemical exchange rate between the agent and water, or the chemical shift of 19F, 31P, 13C or a labile 1H of an agent, which can be used to detect enzyme activity. The variety of agents attests to the creativity in developing enzyme-responsive MRI contrast agents.

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Section: Introductionmentioning

confidence: 99%

Detecting Enzyme Activities with Exogenous MRI Contrast Agents

Hingorani¹,

Yoo²,

Bernstein³

et al. 2014

Chemistry A European J

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“…Despite the advantages of using models in learning [25,28], there are perceived notions that modeling may not be useful as models may be too specific and difficult to generalize [20,29]. These notions may be indirectly refuted by recent efforts promoting the usefulness of modeling in biology [30,31] and by a large volume of studies in other fields [32]. Underpinning the usefulness of modeling is the balance between specificity and generalization.…”

Section: All Models Are Wrong But Some Are Usefulmentioning

confidence: 99%

Of (Biological) Models and Simulations

Ling¹

2016

MOJPB

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All models are wrong, but some are useful. Box and Draper [1].All models are right… Most are useless. Tarpey [2]The role of models has been recognized as an important aspect to the scientific method [3] for more than 70 years [4]. In recent years, there are increasing interests in metabolic modeling in biology [5,6]. The process of building a model is known as modeling. Generally speaking, models can be classified as either material models or formal models. Rosenblueth & Wiener [7] consider material models to be a physical representation of the object under study whereas formal models are symbolic or logical representations of the object under study. For example, a scale down model of an airplane for testing its aerodynamic properties in a wind tunnel is a material model. The main purpose of a scaleddown material model is the ease of study, which had been clearly demonstrated by a study on fireplace more than 200 years ago [8].A formal model, on the other hand, is an abstract but unambiguous description of a physical object or phenomenon, usually in logical or mathematical constructs. Commonly used mathematical constructs for building formal models are rate equations, such as differential equations [9], or state transitions, such as petri nets [10]. Other modeling formalisms had been reviewed by Machado [11]. Besides differentiating models by their underlying formalism, models can also be classified by their informational complexity. At the lowest level, the presence or absence of associations between 2 entities (such as cells or molecules) can be represented as a Boolean term. This results in a binary state petri net or Boolean network, which can be used to study cycles and reachability. For example, a metabolic pathway or gene regulation network is essentially a Boolean network [12]. At the next level, the stiochiometries between each state can be added [13], resulting in a steady state model, which can be simulated and used to study the state or concentrations of various molecules at homeostasis using methods such as flux balance analysis [14][15][16]. At the highest level, the transitions between each state can be represented using a set of differential equations and this result in a kinetic model [17]. The main advantage of kinetic models over steady state model is the ability to simulate each state (or molecules in the context of metabolic modeling) across time, in addition to the ability to model homeostasis [12]. This will allow for identification of bottlenecks in the metabolism [18].With advancements in computing power, formal models, being constructed in mathematical or logical format, render it possible for computation. Such computation or execution of formal models is commonly known as simulation. Hence, by definition, one can "build a model", then "run or execute a model" or "run or execute a simulation" but in no means, one can "build a simulation". The ability to render execution of a model; thus, an executable or simulatable model; defines the fundamental difference between a material model an...

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PBPK Modeling and In Silico Prediction for ADME and Drug–Drug Interaction

Yanni¹

2015

Translational ADMET for Drug Therapy

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Physiologically Based Pharmacokinetic (PBPK) Modeling: Usefulness and Applications

Cited by 3 publications

References 191 publications

Detecting Enzyme Activities with Exogenous MRI Contrast Agents

Detecting Enzyme Activities with Exogenous MRI Contrast Agents

Of (Biological) Models and Simulations

PBPK Modeling and In Silico Prediction for ADME and Drug–Drug Interaction

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