Adventures of Oral Drug - 1

When a oral drug (tablet, capsule etc.) is taken by a patient -
how does it end-up to the place of its action? 
What are the obstacles the drug has to face?
What are the adventures of the oral drug?



The inside lining of the small intestine contains tiny pores [The inner lining of the small intestine has finger-like projections called villus and even smaller projections that are located on these villi are called microvillus. These projections are made of intestinal cells] through which drug is absorbed into the bloodstream via portal veins.  What is more important to remember is - throughout the GI tract, drug has a chance to permeate (cross) gastrointestinal membrane [ABSORPTION]. 

Only when the drug is soluble it can cross the membrane.  Thus, SOLUBILITY is very important.  This is the reason during the drug discovery projects we also would like to measure the solubility and get the solubility data.

To get an idea, if the drug can permeate through the GI membrane - in vitro assays like PAMPA and CaCo-2 are performed. 

What happens next?

Blood in portal veins is unprocessed.  Before entering systemic circulation, all the things blood carries with it have to be processed [whether it is nutrients from food or the drugs]

Blood is processed in Liver.  Here you find lots of different enzymes (from liver microsomes) which can react with the drug.  As mentioned earlier, through-out drug's journey it faces drug-metabolism issues.  It is believed that majority of the drug-metabolism takes place in liver.  This is the reason it is very important to get the liver microsomal stability data [METABOLISM]

Blood from liver enters systemic circulation.  Whatever the unchanged fraction of drug present is now carried forward.