WHY IS ADME SO IMPORTANT? - 3

Some drugs work outside the body (for example, topical antibacterial cream for a skin infection), however most of the drugs have to reach the target inside the body.  We are talking about the drugs which enter the body via ENTERAL route (entering the intestine) like oral, sublingual, rectal and PARENTERAL (bypassing the intestine route) route such as intravenous, subcutaneous, intramuscular. These drugs have to be transported to the target organ via blood i.e. blood transports the drug to the biological target of interest.

As discussed earlier, drug has to pass through four (4) different stages in its lifetime in the body.  These stages are Absorption, Distribution, Metabolism and Excretion (ADME).

What is that we should know about ADME?

ABSORPTION: The word absorption and the amount of drug in bloodstream are related.  Say, when a drug is administered orally we cannot consider it to be fully absorbed until it reaches the bloodstream.  For example, i.v. route does not require absorption – because drug directly enters the blood stream. 

In short entry of the drug into the bloodstream from the site of administration is absorption.

Importantly, absorption depends on chemical stability of the drug, stability of drug to enzymes, proper mixing of drug in the GI tract, passage across GI tract wall to name a few. Interestingly dosage form might disintegrate in the body.

When we talk about absorption – we should understand that the drugs have to cross several hurdles - an oral drug enters from mouth – stomach (Gut) – small intestine – then pass through portal vein to liver – then to blood for circulation through-out the body. 

Most of the drugs are absorbed in small intestine, because – it is the portal (doorway) for absorption of nutrients into blood.  Small intestine is surrounded by a very thin membrane with a large surface area.

DISTRIBUTION: Once the drug is in blood stream, it is moved around the body.  Depending on the affinity these drug molecules might spend some time in an organ, then be carried by the blood to another organ and so on.    

Once the drug crosses the GI track to portal vein to blood stream, this drug in blood is distributed throughout the body.  Moreover, drug in the blood should move into the cell for necessary action. If we are looking at cell receptors as drug targets then cell membrane permeability is not an issue i.e. drug in blood moving into the cell is not necessary.

Therefore, movement of drug from bloodstream to site of action is what distribution means.   It is no surprise that the rate at which drug reaches different organs and tissues will depend on the blood flow to those regions.  For example blood flow is high in heart, lungs, liver, kidneys, brain therefore here equilibration is rapidly achieved.  Skin, bone, fat equilibrate much more slowly.

METABOLISM:  Enzymes or chemicals in the body can alter the drug compound. 

Once ingested, biotransformation of drugs is unsurprisingly a common process.  Therefore, wherever suitable enzymes appear drugs undergo biotransformation.  This can happen in plasma, kidney, lung, gut wall, liver. 

LIVER is ideally placed in the body to capture natural ingested toxins and plays a major role in biotransformation.  Moreover, all of the blood in the body passes through the liver.

Therefore, all kinds of chemical or enzymatic degradation of the drug are what metabolism indicates.

EXCRETION: No confusion here. If the drug is removed from the body without being chemically altered then this process is called excretion.

Both metabolism and excretion together is called Elimination.  (i) Drug can leave the body without being metabolized i.e. no chemical alteration of drug occurs before leaving the body – this is called excretion.  (ii) Drug might be chemically altered (either by chemical reaction or enzymatic reaction) before being excreted from the body (iii) both process (i) and (ii) are together called elimination. 

On the whole, removal of the drug and its metabolites from the body is elimination process.