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Gajewska, M.* ; Paini, A.* ; Sala Benito, J.V.* ; Burton, J.* ; Worth, A.P.* ; Urani, C.* ; Briesen, H.* ; Schramm, K.-W.

In vitro-to-in vivo correlation of the skin penetration, liver clearance and hepatotoxicity of caffeine.

Food Chem. Toxicol. 75, 39-49 (2015)
Verlagsversion DOI PMC
Creative Commons Lizenzvertrag
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
This work illustrates the use of Physiologically-Based Toxicokinetic (PBTK) modelling for the healthy Caucasian population in in vitro-to- in vivo correlation of kinetic measures of caffeine skin penetration and liver clearance (based on literature experiments), as well as dose metrics of caffeine-induced measured HepaRG toxicity. We applied a simple correlation factor to quantify the in vitro and in vivo differences in the amount of caffeine permeated through the skin and concentration-time profiles of caffeine in the liver. We developed a multi-scale computational approach by linking the PBTK model with a Virtual Cell-Based Assay to relate an external oral and dermal dose with the measured in vitro HepaRG cell viability. The results revealed higher in vivo skin permeation profiles than those determined in vitro using identical exposure conditions. Liver clearance of caffeine derived from in vitro metabolism rates was found to be much slower than the optimised in vivo clearance with respect to caffeine plasma concentrations. Finally, HepaRG cell viability was shown to remain almost unchanged for external caffeine doses of 5-400 mg for both oral and dermal absorption routes. We modelled single exposure to caffeine only.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Caffeine ; In Vitro-to-in Vivo Correlation ; Physiologically-based Toxicokinetic (pbtk) Modelling ; Virtual Cell-based Assay; Percutaneous-absorption; Population-dynamics; Organic-compounds; Hair-follicles; Pharmacokinetics; Theophylline; Paraxanthine; Combination; Theobromine; Protein
ISSN (print) / ISBN 0278-6915
e-ISSN 0278-6915
Zeitschrift Food and Chemical Toxicology
Quellenangaben Band: 75, Heft: , Seiten: 39-49 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Oxford
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) PPM-MEX-Molecular EXposomics (MEX)