ABSORPTION: PASSIVE AND ACTIVE TRANSPORT (PERMEABILITY) -1

(1)   During the travel of Oral Drug from mouth to intestine, through-out its journey drug has a chance to get absorbed in to blood and also faces metabolism problem.

(2)   Most of the absorption of the drug takes place in the small intestine. Since the surface area of the stomach (and all other parts starting from mouth to stomach) is much smaller than that of the intestine.  The amount of time that the drugs spend in the stomach (and all other parts starting from mouth to stomach) is less and also the surface area of the stomach is small.

·         For a drug to be absorbed in the intestine some portion of it needs to be dissolved in the intestinal juices which are aqueous.  Even if drug is lipophilic the above said dissolution of drug in the intestinal juices is necessary.  

·         Therefore, in case of partly soluble drugs in water, whatever amount is soluble first gets absorbed and then an equivalent amount of un-dissolved portion of drug becomes soluble which is now ready to get absorbed.  Thus complete absorption will take place.

·         There are bile salts present in the intestine which will aid in solvation of the drug and their resultant absorption. Drugs that are amphipathic have no problem in getting absorbed. There are some drugs that are completely insoluble in water such drugs float as globules in the intestine but the bile salts will emulsify these into small enough particles such that absorption can take place.

·         Some drugs can be absorbed into the system by active transport.

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Once the drug is in the body – it has to cross several barriers to reach the site of action.

Barriers like - Gut wall (passage across GI tract wall), cross lipid barriers / cell wall, blood brain barrier etc.  Therefore, bioavailability of the drug depends on all these parameters.

Let us first understand how the compounds permeate through these barriers or membranes.  What are the different permeation mechanisms? 

·         Drug permeation involves several processes of drug transport across the cell membranes.

·         We know that drugs are most often administered away from their site of action

·         Therefore, drug has to permeate from one compartment to another crossing different barriers and then cell membranes.

·         Drug in the GI tract has to pass through the intestinal membrane.  We are going to talk different assays to predict intestinal permeability.  

·         Drug crosses the membranes and gets into the cell by different mechanisms,

i.                    Passive transport (passive permeability) –MAJOR ABSORPTION PATHWAY

ii.                  Active transport (active permeability) – Carrier mediated transport

Drugs are foreign molecules to the cells.  There are specialized carriers which expel these foreign molecules as they enter the cells.  These are called reverse transporters (efflux transporters).

Below is one more cartoon diagram of the same thing presented above.

TWO most common in vitro assays to obtain permeability data:

Parallel Artificial Membrane Permeation Assay (PAMPA) and Caco-2