Drug Distribution

DRUG DISTRIBUTION

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INTRODUCTION:After entering into the systemic circulation

by any route the drug is subjected to disposition process.

Disposition is a process that tend to lower the plasma concentration of drug.

The two major drug disposition process are 1.Distribution 2. Elimination.

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What is Drug Distribution? It involves the reversible transfer of a drug

between one compartment and another.

In simpler terms, it is reversible transfer of a drug between the blood and the extra vascular fluids and tissues.

It is a passive process whose driving force is the Concentration gradient between blood and Extra-vascular tissues.


How long this Distribution occurs?

This process continues until the Equilibrium is attained.


How does distribution occur:It involves two steps: 1. Permeation of free or unbounded drug present in

blood through the capillary wall and entry into ECF. 2. Permeation of drug present in ECF through

membrane of tissue cells and into the ICF. This depend upon two factors:

(a)rate of perfusion to the extra cellular tissues. (b)membrane permeability of the drug.


Why should distribution occur:The pharmacological action of drug at the

target site depends upon the amount of drug distributed to that site.

So distribution plays a vital role in intensity and duration of drug action.

Many factors will effect the drug distribution in the body


FACTORS EFFECTING DRUG DISTRIBUTION

1.Tissue permeability.

2.Organ or tissue size and perfusion rate.

3.Binding of drugs to tissue components.

4.Miscellaneous.


TISSUE PERMEABILITY:

1. Physicochemical properties of drug like

molecular size, pka and partition coeffecient

2. Physiological barriers to diffusion of drugs.

Tissue permeability of the drug is rate

limited.


PHYSICOCHEMICAL PROPERTIES OF DRUG:

Molecular size

Degree of ionisation

Partition coefficient

Stereo chemical nature

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PHYSIOLOGICAL BARRIERS TO DISTRIBUTION OF DRUG:

1.Simple capillary endothelial barrier.

2. Simple cell membrane barrier.

3. Blood-brain barrier.

4.Blood-CSF barrier.

5.Blood-placental barrier.

6.Blood-testis barrier


BLOOD BRAIN BARRIER:The brain capillaries consists of endothelial cells

which are joined to one another by continuous tight intercellular junctions comprising what is called as the blood brain barrier.

Moreover the presence of special cells called as pericytes and astrocytes forms a solid envelop around the brain capillaries.


So inter cellular transport is blocked.

As a result the drug should pass through the

cells rather than between the cells.

Some specific sites in brain called trigger

areas are useful for distribution of drugs.


A solute may thus gain access to brain via only one of the two pathways.

1. Passive diffusion through the lipoidal barrier.

2.Active transport. Three different approaches are used to promote the

crossing of BBB

1. Use of permeation enhancers(DMSO)

2. Osmotic disruption of BBB with mannitol

3. Use of drug carriers (diohydropyridine redox system)


ORGAN OR TISSUE SIZE AND PERFUSION RATE:Perfusion rate is defined as the volume of

blood that flows per unit time per unit volume of tissue.

The order of perfusion rate of different organs present in body is as follows:

Lungs > kidney > adrenals > liver > heart > brain > muscles > skin > fat > bone.

The larger the size of the organ or tissue greater is the drug distribution to that organ.


WHY THE LARGE AMOUNT OF DRUG IS TAKEN BY SKELETAL MUSCLE ? ? ? ?


Answer is SIMPLE

Because skeletal muscle is

very large organ.


BINDING OF DRUGS TO TISSUE COMPONENTS:

A drug can bind to several components such as

Plasma proteins. Blood cells. Haemoglobin. Extra vascular proteins. Other tissues.


PROTEIN BINDING OF DRUGS:

Protein binding of drug plays a key role in distribution of drug.

Most of the drugs form a protein complex with albumin(blood component)

Protein binding is necessary for efficient absorption and distribution of drug.

While forming a complex with proteins the drug is not altered in any aspect.


MISCELLANEOUS FACTORS:

Age .

Pregnancy.

Obesity.

Diet.

Disease status.

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METHODS FOR DETERMINING THE DRUG DISTRIBUTION:

Drug distribution can be determined by

hypothetical methods. They are: One compartment model. Two compartment model.


PARAMETERS FOR DETERMINING DRUG DISTRIBUTION:

Volume of distribution: It is defined as the

hypothetical volume of body fluid into which a drug is dissolved or distributed. It is denoted by Vd.

Vd = X/C X- amount of drug in the body C- plasma drug concentration


REFERENCES:DM Brahmankar and SB Jaiswal,

biopharmaceutics and pharmaco kinetics a treatise.

Remingtons pharmaceutical sciences, mac pub. Co., easton pensylvania.

Modern pharmaceutics by Banker Marcel Dekker Inc., NY.


Robert E Notary, Biopharmaceutics & Pharmacokinetics- An introduction.

Venkateshulu, Fundamentals of boipharmaceutics & pharmacokinetics, Pharma book syndicate.


Conclusion

Any Queries?

Thank You

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Drug Distribution

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