Rob C. van Wijk , Elke H.J. Krekels , Thomas Hankemeier , Herman P. Spaink , Piet H. van der Graaf
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引用次数: 32
Abstract
Interspecies translation of pharmacological processes needs to improve to reduce attrition in drug development. Systems pharmacology integrates systems biology and pharmacometrics to characterise and quantify system-specific behaviour upon exposure to drugs in different species. The zebrafish is a suitable vertebrate model organism for systems pharmacology, combining high-throughput potential with high genetic homology to higher vertebrates. Zebrafish larvae have been increasingly used for drug screens, but the influence of internal drug and metabolite exposure is hardly studied. Quantifying this internal exposure is essential for establishing both exposure-response and dose-exposure relationships, needed for translation. The zebrafish may also serve as a suitable model species for translational studies on the occurrence of hepatotoxicity and the influence of hepatic dysfunction on drug metabolism.
期刊介绍：
Drug Discovery Today: Disease Models discusses the non-human experimental models through which inference is drawn regarding the molecular aetiology and pathogenesis of human disease. It provides critical analysis and evaluation of which models can genuinely inform the research community about the direct process of human disease, those which may have value in basic toxicology, and those which are simply designed for effective expression and raw characterisation.
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