Drug transporter proteins

Many drugs have been recognized to cross the intestinal epithelial cells via passive diffusion, thus their lipophilicity has been considered important. However, as described above, recent studies have demonstrated that a number of drug transporters including uptake and efflux systems determine the membrane transport process. In this chapter, we provide an overview of the basic characteristics of major drug transporters responsible not only for absorption but also for disposition and excretion in order to delineate the impact of drug transport proteins on pharmacokinetics. 

Table 24.1 Overview of Expression Systems, Advantages and Disadvantages in the Expression of Drug Transport Proteins.

Specific Drug Transporter Proteins (ABC Proteins MDR Proteins)... 

Human plasma contains more than 60 proteins. There are three main proteins associated with the binding of drugs albumin, AAG, and lipoproteins. This article does will not review drug transport proteins of recent interest such as p-glycoproteins, organic anion transporters, and dipeptide transporters, which have been reviewed recently. 

Faber KN, Muller M, Jansen PL. Drug transport proteins in the liver. Adv Drug Deliv Rev 2003 55 107-24. 

Drug transport studies in Caco-2 cells grown on permeable supports are easy to perform under controlled conditions. This makes it possible to extract information about specific transport processes that would be difficult to obtain in more complex models such as those based on whole tissues from experimental animals. When the mRNA expression of drug transporting proteins in Caco-2 cells was compared with... 

Faber, K.N., Muller, M., and Jansen, P.L. (2003) Drug transport proteins in the hver. Advanced Drug Delivery Reviews, 55, 107-124. 

Other examples of polymorphic drug transporter proteins include the dipeptide transporter, organic anion and cation transporters, and L-amino acid transporter. Their effects on drug distribution are the focus of ongoing research. 

A second important family of drug transport proteins are the solute carrier transporters (SLC). SLC proteins play important physiological roles in the transport of nutrients and drugs. SLCs function by one of several mechanisms including facilitated, ion-coupled, and ion-exchange transport. Within each of the 43 SLC subfamilies that have been identified, transporters have at least 20 to 25% amino acid sequence identity. Table 9.3 lists the SLC transport families that play... 

Membrane-bound drug transporter proteins are important in drug resistance. What types of transporters are used in chloroquine resistance and what do they do ... 

Transporters are membrane proteins that control the influx of essential nutrients and ions and the efflux of cellular waste, environmental toxins, and other xenobiotics. Approximately 6% of genes in the human genome encode transporters or transporter-related proteins. Drug-transporting proteins contribute to both therapeutic and adverse effects of drugs (Figure 2-1). 

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