Validation de modèles physiologiques pour simuler la pharmacocinétique de molécules chez le rat en recherche pharmaceutique

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

Utilisation des hépatocytes pour extrapoler les clairances hépatiques et prédire les interactions médicamenteuses

Les données in vitro utilisées actuellement pour prédire les interactions médicamenteuses permettent dans le meilleur des cas d'obtenir des prédictions semi-quantitatives, et restent majoritairement qualitatives (Blanchard et al., 2004). De manière à améliorer la précision des prédictions, la capacité d'hépatocytes en suspension (SH) - en présence ou en absence de sérum - à prédire la clairance hépatique in vivo, a été évalue e en utilisant des hépatocytes de rat (Blanchard et al., sous presse) et des hépatocytes humains (Blanchard et al., sous presse ; Blanchard et al., soumise). Les SH sont un modèle au moins aussi prédictif que les cultures primaires d'hépatocytes (CPC), aussi bien chez le rat que chez l'homme. Les clairances prédites, en SH et en CPC, sont nettement augmentées en présence de sérum. L'utilisation d'hépatocytes humains cryoconservés en suspension (CSH) a également été évaluée. Les clairances obtenues sont similaires à celles obtenues avec les cellules fraîches ( Blanchard et al., sous presse; Blanchard et al., soumise). Les hépatocytes en suspension, frais ou cryoconservés, permettent d'obtenir des résultats globalement similaires aux cultures primaires. Cependant, les clairances ont toujours tendance à être sous-estimées, même en présence de sérum.Prediction of drug-drug interaction based on current apporaches are more of qualitative than quantitative nature (Blanchard et al, 2004). With the aim to improve predictions, the ability of hepatocyte in suspension (SH) - in presence and in absence of serum - were evaluated to predict in vivo hepatic clearance, with rat (Blanchard et al, in press) and human hepatocytes (Blanchard et al, in press ; Blanchard et al, submitted). Clearance predicted from hepatocytes in suspension were similar to those obtained with conventionnal primary culture (CPC), as well with rat than with human hepatocytes. Prediction of clearance obtained both in SH and in CPC are clearly increased in presence of serum. The use of cryopreserved hepatocyte in suspension was evaluated and values of clearance obtained similar to those obtained with fresh hepatocytes ( Blanchard et al., in press ; Blanchard et al., submitted). Results obtained with hepatocytes, as well fresh as cryopreserved hepatocytes, were similar to those obtained with primary culture of hepatocytes. However, clearance still tended to be underestimated, even in presence of serum.BESANCON-BU Médecine pharmacie (250562102) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Physiologically-based kinetic modelling (PBK modelling) : meeting the 3Rs agenda

International audienceThis is the report of the 63rd of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM's main objective, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are relevant to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures that would permit the acquisition of expertise about the state of-the-art of on-animal test development and validation, and the potential for incorporating such alternative tests into regulatory procedures. It was decided that this would be best achieved through a programme of ECVAM workshops, each addressing a specific topic, and at which selected groups of independent international experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best ways forward

Tailoring an in-silico model to the electrophysiology of individual iPSC-derived caradiomyocyte lines: one size fits all?

Poster given at the Safety Pharmacology Society Annual Meeting in Berlin, September 2017.<br

Neuroscience and Education - an Incompatible Relationship

This is the accepted manuscript. The final version is available from Wiley at http://onlinelibrary.wiley.com/doi/10.1111/soc4.12233/abstract.To date there has been little opposition to the growing influence of cognitive neuroscience in education from the education profession itself. However there is growing criticism from the fields of psychology and philosophy. This paper aims to summarize the central arguments found in literature critical of the claims made by cognitive neuroscientists who advocate its potential to improve education. The paper is organised around three sections which draw together assessments from psychology, philosophy and sociology of education. The first, “Brain, Mind and Culture”, lays out the general argument against neuro – education and evaluates two common assumptions made by advocates of neuro-education: that there is a causal relationship between brain and mind; and that learning is a central tenet of education. The second section, “Promises and Problems”, critically considers an example of neuro-educational research, and then goes on to discuss how neuro-education has detrimental consequences for two necessary conditions of liberal subject based education; disciplinarity and pedagogic authority. The final section, “Discourses of Risk, Vulnerability and Optimal Outcomes”, considers wider sociological literature to locate neuro - education within its contemporary cultural context. The paper concludes with a summary of the main philosophical and moral objections to neuro-education