Absorption of drugs

 Absorption is defined as the movement of drug from the site of administration to the target site, through the bloodstream.

The three main factors effecting the rate and extent at which a  drug is absorbed include the environment of the absorption site, chemical composition of drug and the route through which the drug is administered.

Mechanism of drug absorption

Drugs are absorbed from the Gastrointestinal Tract through a number of ways. These include diffusion(passive and facilitated), active transport or endocytosis.

Passive diffusion

Passive diffusion is carried out due to development of concentration gradient across a membrane. The drugs moves from the compartment having the higher concentration of drug to the one having the lower concentration. Passive diffusion does not requires the presence of a carrier. A large number of drugs are absorbed via passive diffusion. The water soluble drug components diffuse through aqueous channels whereas the lipid soluble drug components diffuse through the lipid membrane bilayer.

Facilitated diffusion

Some drug agents require special trans membrane carrier proteins to move across membranes. These are normally the larger molecules which cannot cross the membranes on their own. The carrier proteins undergo structural and conformational changes to facilitate the passage of drugs from higher to lower concentration. This process does not consumes ATP.

Active transport

This type of transport system also includes specialized carrier proteins that transport drug molecules across the membrane. The only difference is that active transport requires energy which is provided by the hydrolysis of ATP. This energy can also aid the movement of drug from lower to higher concentration.

Endocytosis & exocytosis

These processes involves the transport of large sized molecules. In endocytosis, the drug molecule is engulfed by the cell and transported inside. Exocytosis is the opposite process of endocytosis. It is sometimes used to secrete substances from the cell to the outside. Example of drugs transported through endocytosis is Vitamin B12 whereas neurotransmitters move across membranes via exocytosis.

 Factors affecting drug absorption

The various factors which influence the absorption of drug are as follows;

Effect of pH

Drugs could be either weakly acidic or weakly basic. Acidic drugs upon ionization produce a proton and an anion, whereas basic drugs produce a proton and an uncharged base. The movement of drug across the membrane is greater if it is uncharged. The effective absorption of drug can be determined by relative concentrations of the charged and uncharged form of drug. The ratio between these two forms is determined by the pH and strength of weakly acidic and basic drug components and the pKa value. Distribution equilibrium is reached when the drug concentration is equal in all body fluids.

Blood flow to the site of drug absorption

The absorption of drug is greater in the part of body where the flow of blood flow is higher. Since the blood flow to the small intestine is greater than in stomach, absorption is higher in small intestine.

Surface area available for absorption

Higher is the surface area, greater is the rate and extent of absorption. The microvilli in small intestine have greater surface area, this favoring absorption.

Contact time at the absorption site

If the drug moves quickly through the GIT, as in diarrhea, it is not sufficiently absorbed. Same is the case with drugs which take longer time to reach small Intestine and hence is not well absorbed.

Expression of P-glycoprotein

The trans-membrane protein transporter called P-glycoprotein transports drug molecules across cell membrane.  In areas where P-glycoprotein are highly expressed, drug absorption is reduced as it pumps the drug out of the cells. It also causes multi drug resistance.

 Bio availability

Bio availability is a very important factor related to drug absorption. It determines the rate and extent to which a drug is absorbed in the blood circulation after it is administered. For example, if 60 mg of a drug is absorbed in the blood from the 100 mg of administered drug, it means the bio availability of drug is 60%. This determination allows us to calculate the accurate doses of drug for routes other than the intravenous routes of administration. This can be done by comparing the plasma level of a drug that is administered through any other route (other than IV), with the plasma level achieved by the IV administration of the same drug.

Factors affecting bio availability

The factors which affect the bio availability of an administered drug are as follows;

Hepatic first pass metabolism

When a drug is administered via IV route, it is 100% absorbed. Whereas a drug administered via oral route has to undergo hepatic first pass metabolism. It enters the portal circulation before entering the systemic circulation. Rapid metabolism of drug in the liver or GIT leads to decreased availability of drug in the systemic circulation, That is, decreased bio availability of drug, thus a drug with high first pass metabolism should be given in a dose sufficient enough ensure the desired availability of drug to site of action.

Drug solubility

A drug which is purely hydrophilic has poor bio availability as it is unable to cross the lipid membrane bilayer. Similarly, a drug which is purely lipophilic also has poor bio availability as it is completely insoluble in aqueous body fluids. for a drug to be completely absorbed, it must be lipophilic (to enter into the cells of the body), a slightly hydrophilic (to be soluble in aqueous fluids of the body). This is one of the reasons that most of the drugs are really acidic or basic in nature.

Chemical instability

Many drugs become instable in the acidic medium of the stomach ( for example, penicillin G), whereas others require protection from the degradative enzymes present in GIT. The bioavailability of a drug decreases if it is largely effected by the presence of enzymes or chemicals during it's passage from the gut.

Nature of the formulation of drug

Drug absorption may be affected by factors such the particle size of the drug, salt formation property, polymorphism,  presence or absence of enteric coating or presence of excipients. These factors can alter the dissolution of the drug and hence it's bioavailability is also effected.

 Bioequivalance

If two drugs drugs take similar time to achieve peak blood concentration, that is, they have comparable bioavailability, they are said to be bio equivalent.

 Therapeutic equivalence

Two drugs having the same active ingredients, same dosage forms and are administered through the same route,have the same ADRs and same clinical and safety profiles, are known as therapeutically equivalent.

(The terms Bioequivalence and therapeutic equivalence are not interchangeable)