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May, J. E.; Xu, J.; Morse, R.; Avent, N.; Donaldson, C. (2009)
Publisher: Royal Society of Medicine
Languages: English
Types: Article
Prior to introduction to the clinic, pharmaceuticals must\ud undergo rigorous toxicity testing to ensure their safety.\ud Traditionally, this has been achieved using in vivo animal\ud models. However, besides ethical reasons, there is a\ud continual drive to reduce the number of animals used for\ud this purpose due to concerns such as the lack of\ud concordance seen between animal models and toxic effects\ud in humans. Adequate testing to ensure any toxic\ud metabolites are detected can be further complicated if the\ud agent is administered in a prodrug form, requiring a source\ud of cytochrome P450 enzymes for metabolism. A number of\ud sources of metabolic enzymes have been utilised in in vitro\ud models, including cell lines, primary human tissue and\ud liver extracts such as S9. This review examines current and\ud new in vitro models for toxicity testing, including a new\ud model developed within the authors’ laboratory utilising\ud HepG2 liver spheroids within a co-culture system to\ud examine the effects of chemotherapeutic agents on other\ud cell types.
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