Drug transport active

Alternatively, one interesting drug delivery technique exploits the active transport of certain naturally-occurring and relatively small biomacromolecules across the cellular membrane. For instance, the nuclear transcription activator protein (Tat) from HIV type 1 (HlV-1) is a 101-amino acid protein that must interact with a 59-base RNA stem-loop structure, called the traus-activation region (Tar) at the 5 end of all nascent HlV-1 mRNA molecules, in order for the vims to replicate. HIV-Tat is actively transported across the cell membrane, and localizes to the nucleus [28]. It has been found that the arginine-rich Tar-binding region of the Tat protein, residues 49-57 (Tat+9 57), is primarily responsible for this translocation activity [29]. 

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. 

Zhang EY, Phelps MA, Cheng C, Ekins S and Swaan PW. Modeling of active transport systems. Adv Drug Deliv Rev 2002 54 329-54. 

Eischer, H. Passive diffusion and active transport through biological membranes - binding of drugs to... 

Lipinski et al. at Pfizer [11] analyzed the distribution of physicochemical properties of 2245 drugs from the WDI that have entered clinical trials after excluding natural products and actively transported molecules. They proposed the Rule-of-5 to indicate that poor absorption or permeation is more likely when ... 

FIG. 2 Mechanisms of drug transfer in the cellular layers that line different compartments in the body. These mechanisms regulate drug absorption, distribution, and elimination. The figure illustrates these mechanisms in the intestinal wall. (1) Passive transcellular diffusion across the lipid bilayers, (2) paracellular passive diffusion, (3) efflux by P-glycoprotein, (4) metabolism during drug absorption, (5) active transport, and (6) transcytosis [251]. 

Finally, from the available research into the variety of mechanisms for targetting ophthalmic drugs to specific tissues, means for integrating—both figuratively and literally—combinations of effects are now available [15]. Certainly, the combination of hydrodynamics, retention or sustained release, and diffusional or even active transport can be computed, their influence anticipated, and some specific deficiencies addressed. Nonetheless, many unanticipated interactions may often intrude and still leave the field heavily dependent on empirical assessment. 

Drugs absorbed by active transport mechanisms appear to have a delayed rate, but not extent of absorption, in the neonatal period [20]. The absorption of vitamin K depends, to some extent, on the development of intestinal flora. 

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