BY DR FARHEEN SALAHUDDIN

Pharmacokinetics :
There are four phases of P.K
Absorption
Distribution

Metabolism
Excretion
Absorption
Absorption is the transfer of a drug from its site of administration to blood
stream
FACTORS AFFECTING
ABSORPTION
Effect of pH

Blood flow

Surface area

Expression of P- glycoprotein
 1. pH &
 pH of the gastrointestinal fluid & blood may
Ionization
interfere with the absorption of drugs
 Acidic drugs are better absorbed in stomach
 e.g aspirin ( weak acid) remain unionized form in acidic
medium of stomach, it favour their absorption
 Basic drugs ( morphine ) better absorbed in intestine

2. Blood flow:
 Drugs are absorbed most rapidly from sites where
blood flow is high
3:Total surface area
 Drugs absorption is good from large surface area

4: Expression of P glycoprotein
 These are transmembrane transport protein
responsible for transporting various molecules
including drugs,across cell membrane.Expressed in
liver,kidneys,placenta,intestine and brain capillaries,it
pumps out drug.
Absorption & Ionization
Non-ionised drug

More lipid soluble drug

Diffuse across cell

membranes more easily
BIOAVAILABILITY ---It measures the
fraction
(F) of administered dose of a drug that reaches
the systemic circulation in unchanged form.
If BA is 100 %  I.V parenteral dose

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Drug
Distribution
 Drug distribution is the process by which a drug
reversibly leaves the blood stream and enter the
interstitial and cell of the tissues.
Factors affect distribution::
Capillary permeability
Lipid solubility
 Ionization at physiological pH
 Extent of binding to plasma and tissue protein
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Distribution
The movement of
drug from the blood to
and from the tissues
1.Blood flow:
Blood flow to the brain, liver and kidney is greater than
that to the skeletal muscles, whereas adipose tissue has a
lower rate of blood flow.

2.Capillary permeability
Capillary permeability is determined by capillary
structure and by the chemical nature of the
drug.

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a. Capillary structure:

 Inthe brain, the capillary structure is continuous, and

there are no slit junctions. This contrasts
with the liver and spleen, where a large part of the
basement membrane is exposed due to large,
discontinuous capillaries through which large
plasma proteins can pass.

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b.
Blood-brain barrier:
To enter the brain, drugs must pass through the
endothelial cells of the capillaries of the CNS or be
actively transported.
Lipid-soluble drugs readily penetrate into the CNS
because they can dissolve in the membrane of the
endothelial cells.

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c. Drug structure:
 The chemical nature of a drug strongly influences its
ability to cross cell membranes.
 Hydrophobic drugs, readily move across most
biologic membranes.
 Hydrophilicdrugs, do not readily penetrate cell
membranes, and therefore, must go through the slit
junctions.

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3.Binding of drugs to plasma
proteins
Reversible binding of drugs to plasma proteins slows
their transfer out of the vascular compartment.
 ---As the concentration of the free drug decreases
due to elimination by metabolism or excretion, the
bound drug dissociates from the protein.

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VOLUME OF DISTRIBUTION:
Volume that is required to contain the entire drug in the body.

I) Plasma compartment:
Drug has large molecular weight and extensively bind to the plasma
protein
eg: heparin
II) Extracellular Fluid:
Drug has low molecular weight but hydrophlilc
Eg: Aminoglycoside

III) Total body water:

Drug has low molecular weight and lipophilic
Eg : ethanol
Questions :

1. Write brifely on:

1. First pass effect
2. Volume of distribution
3. Bioavailability

2. Define drug distribution. Mention the factor that

affect drug distribution.