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Drug Distribution,Floating Drug Delivary System,FDDS, GMP Guidelines PHARMACOKINETICS,manipal,pharmaceutics,gpat,powerpoint presentations,niper,pharmacy material,pharmacy ppts,entrance exam materials,physical pharmacy,chronopharmacokinetics

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4K views26 pages

Drug Distribution: Visit For More Ppt's & Material

Drug Distribution,Floating Drug Delivary System,FDDS, GMP Guidelines PHARMACOKINETICS,manipal,pharmaceutics,gpat,powerpoint presentations,niper,pharmacy material,pharmacy ppts,entrance exam materials,physical pharmacy,chronopharmacokinetics

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GANESH KUMAR JELLA
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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.
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How long this Distribution
occurs?

This process continues until the


Equilibrium is attained.

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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.

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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

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FACTORS EFFECTING DRUG
DISTRIBUTION

1.Tissue permeability.
2.Organ or tissue size and perfusion rate.
3.Binding of drugs to tissue components.
4.Miscellaneous.

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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.

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PHYSICOCHEMICAL
PROPERTIES OF DRUG:

Molecular size

Degree of ionisation

Partition coefficient

Stereo chemical nature

Pka
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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
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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.

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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.


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 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)

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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.
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WHY
THE LARGE AMOUNT
OF DRUG IS TAKEN
BY SKELETAL
MUSCLE ? ? ? ?
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Answer is SIMPLE

Because skeletal muscle is


very large organ.
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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.

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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.

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MISCELLANEOUS FACTORS:
Age .

Pregnancy.

Obesity.

Diet.

Disease status.

Drug interactions.
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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.

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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
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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.

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Robert E Notary, Biopharmaceutics &
Pharmacokinetics- An introduction.
Venkateshulu, Fundamentals of
boipharmaceutics & pharmacokinetics,
Pharma book syndicate.

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Conclusion
Any Queries?
Thank You

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