Evaluation of research activities and research needs to increase the impact and applicability of alternative testing strategies in risk assessment practice

Punt, Ans; Schiffelers, Marie-Jeanne; Horbach, G. Jean; Sandt, J.J.M. van de; Groothuis, Geny M. M.; Rietjens, Ivonne M. C. M.; Blaauboer, Bas J.

doi:10.1016/j.yrtph.2011.06.007

Cited by 20 publications

(23 citation statements)

References 57 publications

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“…The body and model are represented as actual blood and tissue (usually total body weight) volumes, fractions (f (d)) of cardiac output and systemic or intrinsic clearance [21,22]. Analyzing only blood or plasma concentrations versus time, the minimal-PBPK models parsimoniously generate physiologicallyrelevant PK parameters [22].…”

Section: Pbpk Studiesmentioning

confidence: 99%

Physiologically-Based Pharmacokinetic Model for Plant-Based Anti-Oxidant Drugs

Viswanathan

Tks

Chida³

et al. 2016

Asian J Pharm Clin Res

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Objective: A pharmacokinetic study is a cumbersome process in clinical research. It is very important in target validation and in shifting a lead compound into a drug. Our major objective was to reveal the most important physiochemical characters of the plant-based anti-oxidants in align with human physiology. The in silico studies can preferably be the best solution to identify the physiologically-based pharmacokinetic (PBPK) behavior of the anti-oxidants.Methods: Anti-oxidants are found in many foods including fruits and vegetables. Few of the important anti-oxidants, i.e. around 10 plant-based antioxidant compounds were taken for this research. These compounds were evaluated based on their pharmacokinetic parameters. The properties such as Lipinski's rule of 5, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the compounds were screened thoroughly with the help of tools such as molinspiration and gastroplus. Results:The physiological studies of these compounds had shown different compartmental absorptions of the compound in the human gastrointestinal tract. Certain compounds were found to pass the physiological barriers and had the ability to become a drug. The compounds were filtered using the risk and toxicity factors. These risk factors caused the compounds to fail in the process of becoming a drug. Conclusion:The compounds which passed the PBPK studies were eligible to become a drug. Of the 10 compounds investigated, eugenol, gingerol, zingerone, and geraniol were found to have higher fraction of absorption to become a drug. Out of these compounds, the compounds gingerol and eugenol have shown the best factor of absorption, and hence, have a better probability of becoming a drug.

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Section: Pbpk Studiesmentioning

confidence: 99%

Physiologically-Based Pharmacokinetic Model for Plant-Based Anti-Oxidant Drugs

Viswanathan

Tks

Chida³

et al. 2016

Asian J Pharm Clin Res

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“…eters and interspecies extrapolations for physiologically based toxicokinetics (PBTK) models in chemical risk assessment (Andersen, 2003;Clewell and Clewell, 2008), that can allow extrapolation of in vitro concentration response curves to in vivo dose response curves (Punt et al, 2011).…”

Section: The Importance Of Metabolism In Prediction Of Responsementioning

confidence: 99%

“…The in vitro metabolism data can inform metabolic model parameters of PBTK modeling to assist in the accurate representation of in vivo metabolic processes, both qualitatively and quantitatively. However, the development of more case study research is needed for the further development of proofs of principle for incorporating PBPK modeling (Punt et al, 2011).…”

Section: The Choice Of Species Providing S9mentioning

confidence: 99%

“…PBTK-modelling could contribute to overcoming this limitation by providing a method that allows extrapolation of in vitro concentration-response curves to in vivo dose-response curves. However, while commonly used in drug metabolism research, insufficient examples of proof of principle for chemical risk assessment are available (Punt et al, 2011), although algorithms for predicting partition coefficients into different tissue compartments have been developed for environmental chemicals (e.g., Peyret et al, 2010).…”

Section: Exploration Of the Feasibility Of A Battery Approachmentioning

confidence: 99%

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In vitro metabolism and bioavailability tests for endocrine active substances: What is needed next for regulatory purposes?

Jacobs¹

2013

ALTEX

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“…It is clear that much more experience with these test systems is needed for full integration of in vitro biomarker-derived data into the process of risk assessment (Punt et al, 2011;Gabbert and Benighaus, 2012). However, we can make use of past experiences, such as in the area of pharmaceutical development, where the use of in vitro methods in screening and selecting compounds for their efficacy, and to a lesser extent for their toxicity, has a longer history.…”

Section: Future Research Needs Conclusion and Recommendationsmentioning

confidence: 99%

The use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans

Blaauboer

Boekelheide

Clewell

et al. 2012

ALTEX

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SummaryThe role that in vitro systems can play in toxicological risk assessment is determined by the appropriateness of the chosen methods, with respect to the way in which in vitro data can be extrapolated to the in vivo situation. This report presents the results of a workshop aimed at better defining the use of in vitro-derived biomarkers of toxicity (BoT) and determining the place these data can have in human risk assessment. As a result, a conceptual framework is presented for the incorporation of in vitro-derived toxicity data into the risk assessment process. The selection of BoT takes into account that they need to distinguish adverse and adaptive changes in cells. The framework defines the place of in vitro systems in the context of data on exposure, structural and physico-chemical properties, and toxicodynamic and biokinetic modeling. It outlines the determination of a proper point-of-departure (PoD) for in vitro-in vivo extrapolation, allowing implementation in risk assessment procedures. A BoT will need to take into account both the dynamics and the kinetics of the compound in the in vitro systems. For the implementation of the proposed framework it will be necessary to collect and collate data from existing literature and new in vitro test systems, as well as to categorize biomarkers of toxicity and their relation to pathways-of-toxicity. Moreover, data selection and integration need to be driven by their usefulness in a quantitative in vitro-in vivo extrapolation (QIVIVE). Keywords: biomarker of toxicity, integrated testing strategies, quantitative in vitro-in vivo extrapolations

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Evaluation of research activities and research needs to increase the impact and applicability of alternative testing strategies in risk assessment practice

Cited by 20 publications

References 57 publications

Physiologically-Based Pharmacokinetic Model for Plant-Based Anti-Oxidant Drugs

Physiologically-Based Pharmacokinetic Model for Plant-Based Anti-Oxidant Drugs

In vitro metabolism and bioavailability tests for endocrine active substances: What is needed next for regulatory purposes?

The use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans

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