Drug transporter-mediated

It has been demonstrated that cis- (76) and frarcs-flupentixol (75) (see Fig. 5) inhibited the photo affinity labeling of P-gp by substrate analogues [173] Binding of several MDR modulators, among them TFP (5), to P-gp was shown by means of fluorescence quenching of the MIANS probe [174] or P-gp tryptophan fluorescence [175]. CPZ (9) is likely a P-gp substrate, as was shown in studies of its transport in membrane vesicles obtained from multidrug-resistant CCRF-CEM cells [176], and therefore it was used as a competitive inhibitor of drug transport mediated by P-gp [177]. 

II.I.2.1 Drug Transport Mediated by SLC Transporters Using Eukaryotic Cells 532... 

Drug Transport Mediated by ABC Transporters Using Eukaryotic Membrane Vesicles... 

Drug Transport Mediated by SLC and ABC Transporters Using Double Transfected Cells... 

Another human colonic cancer cell line is T84 this develops monolayers of high TER ( 1000 Q cm2) when grown on permeable supports, but cells are not well differentiated and have been described as resembling a colonic crypt cell phenotype. Hence, these cells have been used mainly in studies of epithelial ion transport and are generally not considered to be adequate for drug transport studies, particularly with respect to carrier-mediated processes [10, 79, 82-84]. 

N. L., Drugs absorption limited by P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers, Pharm. Res. 1993, 10, 743-749. 

M. F., Wilkinson, G. R., Kim, R. B., OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine, Drug Metab. Dispos. 1999, 27, 866-871. 

Susanto, M., Wacher, V. J., Silverman, J. A. et al., Grapefruit juice activates P-glycoprotein-mediated drug transport, Pharm. Res. 1999, 16, 478-485. 

The transporter-mediated uptake of drugs into epithelial cells is emerging as a new trend in biopharmaceutics [6]. Utilization of the intestinal epithelial transporters to facilitate the absorption of drugs or prodrugs appears to be an attractive delivery approach. The purpose of this chapter is to describe the pharmaceutical and medicinal relevances of intestinal transporters. This will provide new knowledge for strategies to enhance intestinal absorption of drugs. 

Grundemann, D., et al. Drug excretion mediated by a new prototype of polyspecific transporter. Nature 1994, 372, 549-552. 

P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers. Pharm. 

The liver plays an important role in determining the oral bioavailability of drags. Drag molecules absorbed into the portal vein are taken up by hepatocytes, and then metabolized and/or excreted into the bile. For hydrophilic drugs, transporters located on the sinusoidal membrane are responsible for the hepatic uptake [1, 2]. Biliary excretion of many drags is also mediated by the primary active transporters, referred to as ATP-binding cassette transmembrane (ABC) transporters, located on the bile canalicular membrane [1, 3-5], Recently, many molecular biological... 

Shitara, Y., Lu, C., Li, A. P., Y. Kato, Y., Suzuki, H., Ito, K., Itoh, T., Sugiyama, Y., Cryopreserved human hepatocytes as a tool for the prediction of in vivo transport and transporter-mediated drug-drug interactions, Abstract of International Conference on Drug Interaction, Hamamatsu, October 21-23, 1999, p. 87. 

Tamai I, Tsuji A. Transporter-mediated permeation of drugs across the blood-brain barrier. J Pharm Sci 2000 89(11) 1371 1388. 

---