Primary hepatocyte cultures as prominent in vitro tools to study hepatic drug transporters. (May 2013)

• Record Type: Journal Article
• Authors: Ramboer, Eva; Vanhaecke, Tamara; Rogiers, Vera; Vinken, Mathieu
• Is Part Of: Drug metabolism reviews. Volume 45:Number 2(2013:Apr.)
• Page Start: 196
• Page End: 217
• Publication Date: 2013-05
• Subjects: Drugs -- Metabolism -- Periodicals; Pharmacokinetics -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; 615
• DOI: 10.3109/03602532.2012.756010
• Languages: English
• ISSNs: 0360-2532

Abstract

<abstract> <title>Abstract</title> <p>Before any drug can be placed on the market, drug efficacy and safety must be ensured through rigorous testing. Animal models are used for this purpose, though currently increasing attention goes to the use of alternative <italic>in vitro</italic> systems. In particular, liver-based testing platforms that allow the prediction of pharmacokinetic (PK) and pharmacotoxicological properties during the early phase of drug development are of interest. They also enable the screening of potential effects on hepatic drug transporters. The latter are known to affect drug metabolism and disposition, thereby possibly underlying drug-drug interactions, which, in turn, may result in liver toxicity. Clearly, stable <italic>in vivo–</italic>like functional expression of drug transporters in hepatic <italic>in vitro</italic> settings is a prerequisite to be applicable in routine PK and pharmacotoxicological testing. In the first part of the article, an updated overview of hepatic drug transporters is provided, followed by a state-of-the-art review of drug-transporter production and activity in primary hepatocyte cultures (PHCs), being the gold-standard <italic>in vitro</italic> system. Specific focus is hereby put on strategies to maintain long-term functional expression, <italic>in casu</italic> of drug transporters, in these systems. In the second part, the use of PHCs to assess hepatobiliary transport and transporter-mediated interactions is outlined.</p> </abstract>