Drug-Induced Liver Injury and Individual Cell Models

摘要: Drug-induced liver injury (DILI) is the most common cause of acute failure and accounts for majority regulatory actions on drugs. Furthermore, DILI a relevant project terminations in pharmaceutical development. The idiosyncratic form especially threat late clinical development phases postmarketing, respectively. Even occurrence only few cases or postmarketing may suffice to terminate withdraw an otherwise promising therapy. Despite advances preclinical assessment dose-dependent toxicity, still big challenge vitro research: it not requires individualized models but also huge number tests. We have developed investigated MetaHeps®, technology involving hepatocyte-like cells generated from peripheral monocytes without genetic modifications. These exhibit several characteristics show donor-specific activities drug-metabolizing enzymes. With MetaHeps we performed investigations patients with suspicion. By investigating derived could increased susceptibility drugs involved individual patients. testing rule out help identify other causes injury. Moreover, identified causative agent polymedicated In conclusion, research cell which produce results comparable situation. suggest as novel tool cope these challenges DILI.