Distribution involves the movement of drugs through the body via absorption, transport through capillaries, penetration of cells, and excretion. The main compartments that the body's water is distributed in are the extracellular, interstitial, intracellular, transcellular, and blood compartments. Factors that affect a drug's distribution include its binding to plasma proteins, the blood flow to different organs, its ability to bind to cells, its concentration in fatty tissues, redistribution from tissues to plasma, and its ability to cross tissue barriers like the blood-brain barrier. A drug's fat-water partition coefficient determines how much it will distribute to fatty tissues versus water-based tissues.

1. Distribution
Distribution: Movement of drug in the body.
Absorption, capillary transport, penetration
into cells and excretion are basic examples
of distribution.
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2. Graphical representation of fate of a drug after absorption:
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3. Distribution compartments: Body water is
distributed into 5 main compartments, shown bellow:
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4. Name of the compartments with %
• Extra cellular compartment, 4.5%
• Interstitial fluid, 16%
• Intracellular fluid, 35%
• Transcellular, 2.5% (CSF, peritoneal, digestive
secretion etc)
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5. List of factors affecting distribution of drugs:
The following factors affect in the distribution of drugs.
1. Binding of drug to plasma protein
2. Rate of blood flow to various organs
3. Cellular binding
4. Concentration in fatty tissue
5. Redistribution
5. Blood brain barrier
6. Permeability across the tissue barrier
7. PH of the distribution media
9. Fat: Water partition coefficient
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6. Binding of drug to plasma protein:
Followings are the features of plasma protein binding.
– Plasma protein binding increases the concentration of drug in blood than
in the extra cellular fluid.
– Bound portion is in equilibrium with free drug. As the unbound fraction
excreted or metabolized, additional drug is dissociated from the protein.
– Protein binding increases the half life as it is not filtrated by glumerular
filtration or not metabolized.
- Protein bound drug does not reach in the site of action and inactive.
- Acidic drug binds with albumin and basic drug binds with α1 -
glycoprotein and β - globulin
- In hypoalbumenemia, toxic effects occur due to deficiency of binding
protein and also for the intense concentration of free drug.
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7. Factors influencing drug - protein bindings:
1. Drug - Physicochemical properties of drug eg, shape, size, physical state etc.
- Total concentration of drug in body
2. The protein:
- Quantity of protein available for binding with drug
- Quality or Physicochemical nature of protein
3. Affinity between drug and protein i.e., the magnitudes of association
4. Drug interactions
- Competition for the drug by other substance at a protein binding site.
- Alteration of the protein that modify the affinity of the drug for the protein.
5. Pathophysiologic condition of the patients
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8. Bonds that are responsible for protein binding are as follows:
i) Hydrogen bond
ii) Ionic bond &
iii) Vander Waals force (weak forces between two
atoms or moles)
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9. Rate of blood flow to various organs
• It affects delivery of drug to various organs.
• Distribution is directly proportional to rate of blood flow. For
example, after IV administration, the concentration of highly
lipophilic compound in a well perfused (Ability of passing and
receiving blood is very high) tissue eg. brain rapidly reaches
equilibrium with unbound drug in plasma. Other well perfused
organs include kidney and liver.
• Distribution is high of drug in this well perfused organs.
• Muscle - less well perfused. Skin, viscera and Fat - limited blood
flow , so takes ups & absorb drug more slowly.
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10. Cellular binding :
• It is the result of drug’s affinity for some cellular
constituents.
• For example , the high concentration of
antimalarial drug quinacrine in liver or muscle is
probably caused by its affinity for nucleoprotein
and phospholipids.
• Large fraction can be bound and may act as a
reservoir & prolongs drug action. 10

11. Concentration in fatty tissue:
• It also affects distribution.
• For example,highly lipid soluble drugs like
glutethimide distribute into fat, which then serves
as a depot. Extraction of such drugs from
plasma by metabolism or excretion results in
egress from fat into blood with restoration of the
circulating concentration.
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12. Redistribution:
• It is a factor in terminating drug effect primarily
when a highly lipid soluble drug that acts on the
brain or cardiovascular system is administered
rapidly by intravenous or inhalation.
• Incase of thiopental anesthetic it is observed.
Due to high blood flow it is reaches with
maximum concentration in brain within a minute.
• With conclusion of injection, the plasma
concentration fall as drug goes to other tissue.
• But the unbound drug from the brain return
back to the plasma and this is the fact of
redistribution. 12

13. Bone and teeth as a reservoir for redistribution:
• The tetracycline antibiotics and heavy metals may
accumulate in bone and teeth due to their affinity for
calcium by adsorption on to the crystal surface and
eventual incorporation into the crystal lattice.
• Bone can become a reservoir for the slow release of
toxic agents such as radium or lead into the blood; the
effects can thus persist long after exposure has ceased.
(The effect will be observe after a long period)
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14. Blood brain barrier :
• The capillaries of Central Nervous System (CNS) are enveloped by
glial cell and the barriers consist of a continuous layer of endothelial
cells joined by tight junction. The brain is consequently inaccessible
to many drugs, including many anticancer drugs and some
antibiotics such as aminoglycosides with a lipid solubility that is
insufficient to allow penetration of the blood brain barrier.
• However inflammation can disrupt (meningeal & encephalic
inflammation) the integrity of blood brain barrier, allowing normally
impermeant substance to enter the brain, consequently penicillin
can be given intravenously to treat bacterial meningitis.
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15. Fat: Water Partition coefficient:
• Fat: water partition coefficient determines how much will
be distributed in fat and how much will be distributed in
water.
• The more will be the value the more will distributed in fat
and the less will be the value of the ratio the less will
distributed in the fat.
• For example, Morphine quiet enough lipid soluble but
lipid: water partition co-efficient is 0.4 and compared with
it thiopental has lipid water partition co-efficient is 10. So
it accumulates in body fat. Vitamin, Carbenicillin &
Vecuronium polar, so not cross cell membrane. So they
remain in ECF (Extra Cellular Fluids)
Ref: Rang & Dale, P- 15

16. Pharmacologically sanctuary sites:
• The sites where drug concentrations are bellow those
necessary to achieve a desired effect even though blood
levels are adequate. This situation apparently occurs
with HIV protease inhibitors and also with loperamide, a
potent, systemically active opoids that lacks any central
effects characteristics of other opoids.Ref: GG-p 10
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