Toward Personalized Medicine with Physiologically Based Pharmacokinetic Modeling

Feng, Kairui; Leary, Robert

doi:10.4155/ipk-2016-0014

Cited by 8 publications

(3 citation statements)

References 18 publications

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“…These questions are the focus of the field of pharmacokinetics (PK). In particular, physiologically-based pharmacokinetic (PBPK) [75] models take into account the individual's biometrics and physiological characteristics (often including genetic variants) to study the absorption, distribution, metabolism and excretion of a drug in the body and consequently predict the concentration of the drug that reaches the target tumor tissue. This is typically combined with a pharmacodynamic model (PD) that describes the effect of the drug on the target cell.…”

Section: Discussionmentioning

confidence: 99%

How to find the right drug for each patient? Advances and challenges in pharmacogenomics

Kalamara

Tobalina

Sáez-Rodríguez

2018

Current Opinion in Systems Biology

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Cancer is a highly heterogeneous disease with complex underlying biology. For these reasons, effective cancer treatment is still a challenge. Nowadays, it is clear that a cancer therapy that fits all the cases cannot be found, and as a result the design of therapies tailored to the patient's molecular characteristics is needed. Pharmacogenomics aims to study the relationship between an individual's genotype and drug response. Scientists use different biological models, ranging from cell lines to mouse models, as proxies for patients for preclinical and translational studies. The rapid development of "-omics" technologies is increasing the amount of features that can be measured in these models, expanding the possibilities of finding predictive biomarkers of drug response. Finding these relationships requires diverse computational approaches ranging from machine learning to dynamic modeling. Despite major advances, we are still far from being able to precisely predict drug efficacy in cancer models, let alone directly on patients. We believe that the new experimental techniques and computational approaches covered in this review will bring us closer to this goal.

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Section: Discussionmentioning

confidence: 99%

How to find the right drug for each patient? Advances and challenges in pharmacogenomics

Kalamara

Tobalina

Sáez-Rodríguez

2018

Current Opinion in Systems Biology

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“…This is achieved through linked differential equations that describe simultaneous or sequential dynamic processes that a drug undergoes in the body. In addition, PBBM predictions can relate to different physiological or disease states, so this unique approach can support personalized pharmacotherapy and drug/dose/dosing regimen selection in different patient populations or individual patients [ 13 , 14 , 15 ].…”

Section: Interpretation Of Oral Drug Dissolution Permeation and Absor...mentioning

confidence: 99%

Model-Informed Drug Development: In Silico Assessment of Drug Bioperformance following Oral and Percutaneous Administration

Djuris,

Cvijic,

Djekic

2024

Pharmaceuticals

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The pharmaceutical industry has faced significant changes in recent years, primarily influenced by regulatory standards, market competition, and the need to accelerate drug development. Model-informed drug development (MIDD) leverages quantitative computational models to facilitate decision-making processes. This approach sheds light on the complex interplay between the influence of a drug’s performance and the resulting clinical outcomes. This comprehensive review aims to explain the mechanisms that control the dissolution and/or release of drugs and their subsequent permeation through biological membranes. Furthermore, the importance of simulating these processes through a variety of in silico models is emphasized. Advanced compartmental absorption models provide an analytical framework to understand the kinetics of transit, dissolution, and absorption associated with orally administered drugs. In contrast, for topical and transdermal drug delivery systems, the prediction of drug permeation is predominantly based on quantitative structure–permeation relationships and molecular dynamics simulations. This review describes a variety of modeling strategies, ranging from mechanistic to empirical equations, and highlights the growing importance of state-of-the-art tools such as artificial intelligence, as well as advanced imaging and spectroscopic techniques.

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“…PK had its origins in the mid-twentieth century (Wagner 1981 ) and as the field matured, grew, and became well accepted, pharmacokinetic understanding led to numerous medical advancements. To list just a few, these include understanding the kinetic determinants of drug sensitivity and resistance (McCallum and Sloan 2017 ), the development of sophisticated methods of drug delivery that ensure effective concentrations of medication at the therapeutic target organ or tissue while reducing the administered dose required for efficacy (Glassman and Muzykantov 2019 ), the development of pharmacogenomics (Nakajima and Yokoi 2005 ) and individualized pharmacotherapy (Magliocco et al 2020 ), and the possibility of reducing drug development costs through pharmacokinetic modeling and simulation (Feng and Leary 2017 ). Although beyond our scope to elaborate further, it would be difficult to overstate the importance of pharmacokinetics to modern pharmacotherapy.…”

Section: Introductionmentioning

confidence: 99%

Principles of dose-setting in toxicology studies: the importance of kinetics for ensuring human safety

Borgert

Fuentes

Burgoon³

2021

Arch Toxicol

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Regulatory toxicology seeks to ensure that exposures to chemicals encountered in the environment, in the workplace, or in products pose no significant hazards and produce no harm to humans or other organisms, i.e., that chemicals are used safely. The most practical and direct means of ensuring that hazards and harms are avoided is to identify the doses and conditions under which chemical toxicity does not occur so that chemical concentrations and exposures can be appropriately limited. Modern advancements in pharmacology and toxicology have revealed that the rates and mechanisms by which organisms absorb, distribute, metabolize and eliminate chemicals—i.e., the field of kinetics—often determine the doses and conditions under which hazard, and harm, are absent, i.e., the safe dose range. Since kinetics, like chemical hazard and toxicity, are extensive properties that depend on the amount of the chemical encountered, it is possible to identify the maximum dose under which organisms can efficiently metabolize and eliminate the chemicals to which they are exposed, a dose that has been referred to as the kinetic maximum dose, or KMD. This review explains the rationale that compels regulatory toxicology to embrace the advancements made possible by kinetics, why understanding the kinetic relationship between the blood level produced and the administered dose of a chemical is essential for identifying the safe dose range, and why dose-setting in regulatory toxicology studies should be informed by estimates of the KMD rather than rely on the flawed concept of maximum-tolerated toxic dose, or MTD.

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Toward Personalized Medicine with Physiologically Based Pharmacokinetic Modeling

Cited by 8 publications

References 18 publications

How to find the right drug for each patient? Advances and challenges in pharmacogenomics

How to find the right drug for each patient? Advances and challenges in pharmacogenomics

Model-Informed Drug Development: In Silico Assessment of Drug Bioperformance following Oral and Percutaneous Administration

Principles of dose-setting in toxicology studies: the importance of kinetics for ensuring human safety

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