Vectorial drug transport

Multidrug Resistance Proteins and Drug Transport 346 Role of P-Glycoprotein for Drug Disposition 349 Vectorial Drug Transport 352 References 355... 

Ito K, Suzuki H, Horie T, et al. Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport. Pharm Res 2005 22 1559-1577. 

Polarized tissues directly involved in drug absorption (intestine) or excretion (liver and kidney) and restricted drug disposition (blood-tissue barriers) asymmetrically express a variety of different drug transporters in the apical or basolateral membrane resulting in vectorial dmg transport. This vectorial dmg transport is characterized by two transport processes the uptake into the cell and subsequently the directed elimination out of the cell (Figure 15.3). Because the uptake of substances... 

Flgure 1, Schematic principle of vectorial drug evasion in liver and kidney. Phase 0 = drug uptake out of blood, Phases 1 and 2 = biotransformation exemplified by hydroxylation and glu-curonidation. Phase 3 = transport ofxenobiotics/metabolites towards excretion. Phase 4 = efflux into excreted fluids and/or backward into blood. Adapted with permission from [43]. 

Figure 11.5 Vectorial transcellular transport of pravastatin, its basal-to-apical transcellular drugs in double-transfected cells, (a) The double- transport is significantly higher compared to the transfected cells expressing OATP1B1 (uptake apical-to-basal transport [177]. (b) Prediction of transporter) on the basal side and MRP2 (efflux in vivo biliary clearance of several bisubstrates of transporter) on the apical side have been rat Oatplb2 and Mrp2 from their in vitro...

In the renal epithelium, many uptake transporters are localized in the basolateral membrane and efflux transporters are localized in the apical membrane (Figure 15.2). As a result, vectorial transport of endogenous substances and of drugs from the blood into the urine is achieved. The important uptake transporters are members of the SLC22 family of solute carriers, especially the family members OCT2 and OAT2, which are highly expressed in human kidney. 

For example, some SLC on the sinusoidal (basolateral) membrane of hepatocytes take up organic anions, while the ABC on the apical membranes of bile canicular cells excrete them. The combined activities of these two transporters thus results in the vectorial transport of drugs from the blood to the bile. Similarly, the basolateral transporters of the kidney tubular cells act in a coordinated, vectorial manner with apical transporters to secrete organic cations (OCs) from the blood to the urine. 

The SLC transporters mediate either drug uptake or efflux, whereas ABC transporters mediate only unidirectional efflux. Asymmetrical transport across a monolayer of polarized ceUs, such as the epithelial and endothelial cells of brain capillaries, is called vectorial transport (Figure 2-5). Vectorial transport is important in the efficient transfer of solutes across epithelial or endothelial barriers it plays a major role in hepatobiliary and urinary excretion of drugs from the blood to the lumen and in the intestinal absorption of drugs and nutrients. In addition, efflux of drugs from the brain via brain endothelial cells and brain choroid plexus epithelial cells involves vectorial transport. 

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