Pharmacokinetics – Absorption, Distribution, Metabolism and Elimination

Pharmacokinetics

Pharmacokinetics is the quantitative study of drug movement in through and out of body. Pharmacokinetics is the learn about of how drugs are absorbed, distributed, metabolized and eradicated by using the body. It focuses on understanding the processes that determine the rate and extent of drug absorption, distribution, metabolism and elimination.

It involves for process:

1. Absorption of drugs

It is defined as the moment of drug molecules from its site of administration to the systemic circulation. It is a first and important step of pharmacokinetics. When we take any drug through oral rout, it goes into a stomach in which disintegrate and dissolution take place, then drug reach into intestine. After dissolution drug absorb into blood from intestine/stomach through membrane.

Mechanism of absorption

1. Active transport

A primary active transport in this process there is direct ATP requirement. The process transfers only one ion or molecule and in only one direction and hence called as absorption of glucose. In this transport, drug molecules move against the concentration of gradient.

2. Passive transport

Passive diffusion is the process by which molecules spontaneously diffuse from a region of higher concentration, ex- outside of the cell. To a region lower concentration, ex- inside of the cell and it is the main mechanism for passes of drug through membranes.

Liquid soluble drug penetrates the lipid cell membrane with and can pass the cell membrane by passive diffusion.

3. Cellular transport

The movement of food particle from blood to cell and from cell to blood is called cellular transport. By the use of cellular transport the chemical substituent which is absorbed in blood is moves into cell and the waste substituent moves from cell to blood.

Factor affecting drug absorption.

Drug absorption is depending upon following factor:

1. Physiochemical properties of drugs

Particle size

The absorption of drug is inversely proportional to the particle size as well as the particle size of a drug is increasing the rate of absorption is decreases and when the particle is decreases then the rate of absorption is increases.

Solubility

The rate of absorption of any drug is also depends upon the solubility factor because our gastric media is hydrophilic in nature so hydrophilic drug more easily can dissolve into the gastric HCl then lipophilic drug. So, the rate of absorption is high for hydrophilic drug and the rate of absorption is low for lipophilic drug.

Salt from of drug

The strong acidic than a strong basic drug can easily dissociated into the solvent. So they are dissolution rate and absorption rate is very high but in the case of weak acid and weak base drug their dissociation rate is slow. So they absorb very slowly but when we convert the weak acidic and weak basic drug into salt form then their rate of dissociation is increases many times and their rate of absorption is also increases.

Ionization rate

Those drugs which are in ionic form they can be dissolve easily but they can’t cross the cell membrane but in the case of non-ionic form of drug they cannot dissociated easily but they are rate of absorption is high. So, we make any drug is such a way at the time of dissolution they are in ionic form and at the time of absorption they should be in non-ionic form.

2. Gastric implying time

The absorption of drug is also depending upon the gastric emptying time. The drug whose gastric emptying time is less their rate of absorption is high.

3. Drug stability and pH of GIT

There are lots of drop which are soluble in acid or stable in gastric acid, they can be given easily and their rate of absorption is high but in the case of certain drug which do not dissolve into gastric acid and which becomes disintegrated or becomes deactivated in acidic mediums they are uses in certain polymer form and they dissolve into the intestine and their rate of absorption is increase.

4. Surface area

Surface area of any body is directly proportional to the rate of absorption. If the surface area is increases, then the more number of drug will be absorb proper.

5. Blood flow

The rate of drug absorption is directly proportional to the blood flow. When the blood flow in body is increase then the rate of drug absorption is also be increase.

6. Effect of food

The rate of drug absorption is also depending upon the food which is present in the stomach. If the food is present in stomach, then it dilutes the drug and rate of absorption will decrease.

7. First pass metabolism

When the drug directly goes into the liver without reaching into the receptors and systemic circulation, this is called first pass metabolism. For these drug which first pass metabolism is high the rate of drug absorption of slow.

Nature of dosage form

The rate of drug absorption is also depending upon the nature of dosage form. If the drug is taken in orally then some part of drug is metabolized so their rate of absorption is slow but when the drug is given parenterally their bioavailability is 100% and rate of absorption is 100%. In the case of oral the absorption of liquid dosage form is greater than solid dosage form.

2. Distribution of drugs

The distribution of drug is defined as the movement of drug into different compartments of our body. First of all, the drug mixed in the blood and goes ECF extra cellular fluid and then into intra cellular fluid and then after blind with the receptor and give different-2-responce.

Distribution is very important for pharmacokinetics because it is responsible for the pharmacological action of any drug because when the drug can’t bind with the receptor that it can’t produce any pharmacological action response.

Steps of distribution

Steps of distribution is of following three steps.

Step-1: – In step first after the absorption drug is comes into the blood and some parts of drugs is combine with the plasma proteins.

Step-2: – In the form of plasma protein complex the drug reaches into the ECF.

Step-3: – In the step this the free form of drug pass cell membrane and after passing the cell membrane, it reaches into the ECF intracellular fluid & bind with the receptor and gives pharmacological response.

Factor affecting distribution.

There are following factor of affecting distribution.

1. Tissue permeability

Physiological properties

The distribution of drug is also depending upon the physiochemical property of drug like it PKA value, its pH value, its particle size, its acidic nature.

Molecular size

The molecular size is approx. 500 to 600 Dalton is important for the distribution of the drug. If the molecular size is greater than 600 Dalton, then it can’t pass the cell membrane and the distribution is not possible.

Partition coefficient

Drugs are generally hydrophilic or lipophilic nature. If drugs are lipophilic in nature they can cross the cell membrane simply because our membrane is made up from phospholipid and cellulose. If the drugs are hydrophilic in nature, they can’t cross the cell membrane simply.

Degree of ionization

For the better distribution of drug degree of ionization of the drug, it should be law.

2. Physiological barrier

Physiological barrier are those organs which inhibit the free movement of frog into organ directly. It decreases the rate of absorption and rate of distribution. The nature of physiological barrier is different in different-2-organ. It is of following type:

Simple capillary endothelial barrier

This is the simplest type of barrier because in the blood vessel inner wall is made up of endothelial and in blood vessels small pores are present and drug can pass only these pores and can’t pass other than pores. If the particle size of molecule is more than 6000 Dalton then particle cannot pass, these spores and they cannot be absorb from distributed from blood to any organ.

Simple cell membrane barrier

The simple cell membrane barrier is present between the endothelial layer of blood vessel and the cell membrane of any cell. In the various only the drug particle size is 50 to 600 Dalton can pass and the larger particle cannot pass.

Blood brain barrier

The barrier between blood vessels and brain is called blood brain barrier. The blood brain barrier basically barrier are the combination of endothelial cell of blood of brain and manage of the brain. Blood brain barrier is very highly specific in nature because the endothelial layer, which is present in the blood vessels of brain, they are highly specialized and they have light functions and the pores size is very small.

Blood placenta barrier

A semipermeable membrane made up of placental tissues and limiting, the kind of amount of material exchanged between mother and fectus. On a structural basis, the barrier effect of ground by the syncytiotrophoblast continuity, and by basal and plasma membrane electrical charges and by basement membrane. The aqueous phase continuity for diffusion operates  through intracellular gap, fenestrations and transcellular channels.

Blood testes barrier

In the blood testes barrier, there are law such endothelial barrier is present only the drug is pass through the cells by diffusion/osmosis process.

3. Plasma protein binding

Albumin

This is the largest protein which is present in the blood plasma and about 59% concentration of this protein is present in the blood plasma and about 65000 types of drug receptors and present in this protein.

Alpha glycoprotein

Alpha glycoprotein is the second largest protein of blood plasma and in this protein basically proteins nature or glucose in nature molecule are banded. They basically banned of the drug: imipramine, lidocaine, propenal and quinidine.

Lipoprotein

Lipoproteins are a type of molecule that transports lipids (fats) and cholesterol throughout the body. They are composed of a combination of proteins and lipids, which makes them hydrophobic (water-repelling) and able to move through the bloodstream.

Globulin

Globulin is a group of proteins found in the blood and other bodily fluids. It is composed of several types of proteins, including albumin, alpha-globulins, beta-globulins, gamma-globulins and immunoglobulins. Globulin plays an important role in the body’s immune system by helping to fight off infection and disease. It also helps to transport nutrients throughout the body and helps to regulate water balance in cells.

3. Metabolism of drugs

Drug metabolism is also known as bio transformation in metabolism process the active drug is convert into the action form and the polarity of drug is increase, so it removes from receptor.

Drug metabolism is completely into two phase:

1. Phase-1-metabolism

In this phase the main target of metabolism is to increase the polarity of the drug convert active drug into inactive form. In this phase different chemical reaction is perform with the drug, so the polarity of drug is increases and it becomes of water soluble in the phase following reaction is performed. Reaction: – oxidation, reduction, nitration, sulphonating and halogenation.

2. Phase-2-metabolism

In this phase the shape of actual drug is change, so the drug is removed from the receptor and response of drug is stop. The major site of drug metabolism is in liver because different two enzymes are present in the liver which bind with the drug and change the shape of drug.

4. Elimination of drugs

Elimination or excretion is the last step of pharmacokinetics of drugs. In this step after the metabolism inactive form of drug is present in the blood and by elimination process in active form of drug is removed outside from the body.

Elimination organs

The main elimination organs are kidney, and the blood is becomes a with the urine by the elimination process but some of the other excretory organs also works like lungs, liver, skin.

Types of elimination

1. Renal elimination

It is most abundant type of elimination and about 80% drug eliminated through kidney by this renal elimination process.

2. Enterohepatic elimination

When some drugs are eliminated through the liver this is called enterohepatic elimination. Those drugs which have the smallest molecular size they can easily crossed, the liver and reach into the bile acid and their release from the body in the form of bilirubin and biliverdin.

3. Pulmonary elimination

Pulmonary elimination is the smallest parts of drug some amount of drug is eliminate in the form of CO2 from our lungs.

4. Sweat and saliva elimination

When the drug is removed in the form of sweat and saliva, this is called sweat and saliva elimination.