Hepatotoxicity and hepatic metabolism of available drugs: current problems and possible solutions in preclinical stages.
IMPORTANCE OF THE FILED: According to a 2006 survey report of pharmaceutical companies, hepatotoxicity was ranked first in terms of adverse events and it remains the most common reason for restriction or withdrawal of a drug from the market by the FDA. Although there are many reasons underlying drug-induced hepatotoxicity, one of the most important is hepatotoxicity induced by drug metabolites.


METHODS
This review highlights the unexpected evidence showing that > 64 allopathic drugs out of 900 can induce potentially life-threatening hepatotoxicity with diverse clinical features. In parallel, we demonstrate the use of a two-compartment organotypical model for monitoring drug biotransformation and the status of parent drugs or drug metabolites (reactive or stable metabolites).


RESULTS
The reader will gain knowledge of the importance of the two-compartment model with special reference to drug metabolites and become aware of the hepatotoxicity of a list of allopathic drugs, many of which are presently used without prescription.


CONCLUSIONS
A central challenge regarding drug-induced hepatotoxicity is to understand drug metabolite formation because, although many parent drugs are not toxic, their metabolites can be toxic to liver cells following biotransformation.
Giri
Shibashish
S
Biomedical-Biotechnological Center, Department of Cell Technologies, Leipzig, Germany. shibashi@rz.uni-leipzig.de
Nieber
Karen
K
Bader
Augustinus
A
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism
D004364:Pharmaceutical Preparations