In silico and in vitro modeling of hepatocyte drug transport processes: importance of ABCC2 expression levels in the disposition of carboxydichlorofluroscein.

ABSTRACT: The impact of transport proteins in the disposition of chemicals is becoming increasingly evident. Alteration in disposition can cause altered pharmacokinetic and pharmacodynamic parameters, potentially leading to reduced efficacy or overt toxicity. We have developed a quantitative in silico model, based upon literature and experimentally derived data, to model the disposition of carboxydichlorofluroscein (CDF), a substrate for the SLCO1A/B and ABCC subfamilies of transporters. Kinetic parameters generated by the in silico model closely match both literature and experimentally derived kinetic values, allowing this model to be used for the examination of transporter action in primary rat hepatocytes. In particular, we show that the in silico model is suited to the rapid, accurate determinat

SUBMITTER: Howe K 

PROVIDER: S-EPMC2680525 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature