TY - JOUR T1 - Age-dependent Activity of the Uptake Transporters Ntcp and Oatp1b2 in Male Rat Hepatocytes: From Birth till Adulthood JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.114.059212 SP - dmd.114.059212 AU - Sarinj Fattah AU - Patrick P Augustijns AU - Pieter P Annaert Y1 - 2014/01/01 UR - http://dmd.aspetjournals.org/content/early/2014/10/10/dmd.114.059212.abstract N2 - Recognition of the role of hepatic drug transporters in elimination of xenobiotics continues to grow. Hepatic uptake transporters, such as for instance hepatic isoforms of the Oatp (Organic anion transporting polypeptide) family as well as the bile acid transporter Ntcp (Na+-taurocholate co-transporting polypeptide) have been studied extensively both at the mRNA and protein expression levels in adults. However, in paediatric/juvenile populations there continues to be a knowledge gap about the functional activity of these transporters. Therefore, the aim of this study was to examine the functional maturation of Ntcp and Oatp isoforms as major hepatic transporters. Hepatocytes were freshly-isolated from rats aged between birth and 8 weeks. Transporter activities were assessed by measuring the initial uptake rates of known substrates: taurocholate (TCA) for Ntcp and sodium fluorescein (NaFluo) for Oatps. Relative to adult values, uptake clearance of TCA in hepatocytes from rats aged 0, 1, 2, 3 and 4 weeks reached 19, 43, 22, 46 and 63%, respectively. On the other hand, Oatp-mediated NaFluo uptake showed a considerably slower developmental pattern: uptake clearance of NaFluo in hepatocytes from rats aged 0, 1, 2, 3, 4 and 6 weeks were 24, 20, 19, 8, 19 and 64%, respectively. Maturation of NaFluo uptake activity correlated with the previously reported ontogeny of Oatp1b2 mRNA expression, confirming the role of Oatp1b2 for NaFluo uptake in rat liver. The outcome of this project will help in understanding and predicting age-dependent drug exposure in juvenile animals and will eventually support safe and more effective drug therapies for children. ER -