Cultured hepatocytes as investigational models for hepatic toxicity: practical applications in drug discovery and development

Toxicology Letters
Roger G UlrichE L Sun

Abstract

Drugs can fail at any phase during discovery, preclinical or clinical development due to unacceptable levels of toxicity, and liver is commonly the principle target organ. Investigational toxicology methods, using appropriate models and hypotheses, can often resolve problems, identify toxic chemical substituents and salvage therapeutic discovery programs. While in vivo models are used to investigate hepatic drug effects in the context of toxicokinetics and systemic influences, cell culture models provide in vitro systems for investigating specific mechanisms in a precisely controlled environment. Using primary hepatocytes isolated from laboratory animals, we have explored several drug-induced hepatic disorders that surfaced during different phases of drug discovery and development. Additionally, the use of human hepatocytes has allowed us to address concerns for human exposure, examine human relevance of animal data, and provide perspective on problems encountered in clinical trials.

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Citations

Oct 27, 2004·Archives of Toxicology·Christian Grosse-SiestrupDavid A Groneberg
Oct 18, 2000·Toxicology in Vitro : an International Journal Published in Association with BIBRA·K Zierold
Nov 6, 2003·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Jeffrey F WaringRoger G Ulrich
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