Passage of drugs through cell membranes (absorption):

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  Drug absorption necessitates passage of the drug through various cell 

membranes, including cellular plasma membranes and intracellular membranes like 

nuclear membrane or endoplasmic reticulum.  

  Passage of drugs through cell membranes takes place through one of the 

following pathways: 

1- Passive diffusion and partitioning:  

  Within  the cytoplasm or in interstitial fluid, most drugs undergo transport by 

simple passive diffusion  according to Fick's Law of diffusion, where the rate of 

passage of the drug through cell membrane is directly proportional to the 

concentration gradient of the drug across cell membrane.  

  Passive drug transport across cell membranes involves successive partitioning 

of a solute between aqueous and lipid phases  and diffusion within the respective 

phase. The rate of drug transport depends on both pH, lipid/water partition coefficient 

and surface area of absorption site.   

2-Paracellular transport: 

  This is diffusion and transport of the drug molecules and accompanying water 

across narrow junctions between cells or trans-endothelial channels.  

3- Carrier-mediated transport: 

  This includes active transport and facilitated diffusion. In both types, the drug 

is carried by a carrier selective for the drug which is either an endogenous substance 

or similar to an endogenous agent. The carrier system becomes saturated at high drug 

concentration. The process is competitive as drugs with similar structure compete for 

the same carrier.  

  The difference between the two types is that active transport takes place 

against the concentration gradient and necessitates energy. Facilitated diffusion, on 

the other hand take place along the concentration gradient and does not require 

energy.  

4- P-glycoprotein-mediated efflux: 

  P-glycoproteins are embedded in the lipid bilayers of cell membranes in α-

helical domains.  These proteins are ATP-dependent pumps which  facilitate drug 

efflux from the cell. These glycoproteins are often associated with metabolizing 

enzymes to degrade the drug.  Examples  of drugs affected much by these 

glycoproteins are digoxin, nifedipine and cyclosporin.  

5- Vesicular transport: 

  This is the process of engulfing particles or dissolved materials by a cell. This 

includes: 

  Pinocytosis, which is the engulfment of small solutes or fluids.  

  Phagocytosis, which is the engulfment of large particles or macromolecules, 

usually by phagocytes.  

  Exocytosis, which is the movement of macromolecules out of the cell.  

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