Document Detail

Biotransformation of diazepam in a clinically relevant flat membrane bioreactor model using primary porcine hepatocytes.
MedLine Citation:
PMID:  20618872     Owner:  NLM     Status:  In-Data-Review    
In vitro biotransformation of drug using commercial culture medium with serum may not be the ideal culture medium for clinical application in extracorporeal bioartificial liver support (BAL) systems. In these systems, patient's blood or plasma is plumbed to primary hepatocytes within a seeded bioreactor, creating interaction between plasma and seeded hepatocytes. To address this situation, we investigated the biotransformation potential of diazepam in primary porcine hepatocytes with a flat membrane bioreactor (FMB); we used human plasma exposure and serum-free media in organotypical double gel culture model for long-term culture. We investigated diazepam clearance and all major metabolites of diazepam, such as oxazepam, temazepam, and desmethyldiazepam, in conventional single gel and organotypical sandwich models and compared them to the FMB model. Diazepam elimination was higher in double gel cultures with exposure to both SF 3 medium conditions and plasma, when compared to the single gel model in a Petri dish. It was observed that in the FMB, diazepam elimination was stable at about 3 pg/h/cell in plasma and SF 3 exposure. Oxazepam synthesis in the bioreactor was approximately one quarter less than in the Petri dish, but there were no differences between N-desmethyldiazepam and temazepam synthesis in double gel culture. In the flat membrane bioreactor, there was no decrease in the biotransformation of diazepam in plasma exposure compared with the control group. Our results suggest that this plasma exposure bioreactor may offer a useful approach in clinical use of extracorporeal BAL, as well as for drug metabolite investigation into toxicological research.
Michael Maringka; Shibashish Giri; Karen Nieber; Ali Acikgöz; Augustinus Bader
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Fundamental & clinical pharmacology     Volume:  25     ISSN:  1472-8206     ISO Abbreviation:  Fundam Clin Pharmacol     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-04-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8710411     Medline TA:  Fundam Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  343-53     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.
Centre for Biotechnology and Biomedicine, Department of Cell Techniques and Applied Stem Cell Biology, University of Leipzig, Deutscher Platz 5, D-04103 Leipzig, Germany Department of Vascular Surgery, Diakoniekrankenhaus Henriettenstiftung, Marienstraße 72-90, D-30171 Hannover, Germany Institute of Pharmacy, Pharmacology for Natural Sciences, University Leipzig, Talstrasse 33, 04103 Leipzig, Germany.
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