The document discusses drug distribution, explaining the processes of distribution and elimination that affect plasma drug concentration after systemic entry. It outlines factors influencing drug distribution, including tissue permeability, molecular size, pKa, and various physiological barriers. Additionally, it emphasizes how drug ionization and physiological conditions impact drug entry into cells.

1. DRUG
DISTRIBUTION
By
C.Sangavi
Assistant Professor
Department of Pharmaceutics
ABMRCP, Bangalore.

2. • After entry into the Systemic
Circulation, Either by IV or by
Absorption from an oral or
extravascular site, the drug is subjected
to several Processes called Disposition
processes

3. Definition
of
Disposition
Two Major types
Distribution Elimination
The processes that tend to lower
the plasma concentration of the
drug.

4. DISTRIBUTION – This involves
the reversible transfer of a drug
between compartments.
ELIMINATION – This causes
irreversible loss of drugs from the
body.
1. Biotransformation
2. Excretion

5. Interrelationship
between different
process of Drug
Disposition

6. DISTRIBUTION
As per the definition,
One compartment is
always a Blood or
Plasma
Another compartment
is Extravascular fluids
and other Body tissues

7. DISTRIBUTION
MOA - PASSIVE PROCESS DRIVING FORCE –
CONCENTRATION GRADIENT
B/W BLOOD AND
EXTRAVASCULAR TISSUES.

8. STEPS IN DRUG
DISTRIBUTION
Intracellular Fluid
Extracellular Fluids
Blood
1 2

9. 2 steps are
involved in this
Process
2nd Step is the Rate limiting step and depends upon the
Two major factors:
1. Rate of Perfusion to the ECF
2. Membrane permeability of the Drug

10. FACTORS AFFECTING THE
DISTRIBUTION OF DRUG
1. Tissue permeability of Drugs
a. Physiochemical Properties of Drugs
• Molecular Size
• pKa, o/w Partition Coefficient
b. Physiological Barriers to Distribution of Drugs
• Simple carrier endothelial barrier
• Simple cell membrane barrier
• Blood-Brain Barrier
• Blood – Cerebrospinal Fluid barrier
• Blood placental barrier
• Blood Testis Barrier

11. FACTORS AFFECTING THE
DISTRIBUTION OF DRUG
2. Organ/Tissue site Perfusion Rate
3. Binding of Drugs to Tissue components
a. Binding of Drug to Blood components
b. Binding of Drugs to extracellular components
4. Miscellaneous
a. Age
b. Pregnancy
c. Obesity
d. Diet
e. Disease State
f. Drug Interactions

12. Tissue permeability
of Drugs
• This permeability depends on the Physiochemical
properties of the drug like Molecular Size and pka
value as well as Physiological Barriers that restrict the
diffusion of the drug into tissues.

13. PHYSIOCHEMICAL
PROPERTIES OF
THE DRUG
Molecular Size
The capillary membrane is easily crossed by almost
all medications with a molecular weight of less than
500–600 Daltons, allowing them to diffuse into
extravascular interstitial fluids.
However, the molecular size, ionization constant,
and lipophilicity of the medicines all affect how well
they penetrate cells from the ECF.
Only tiny, water-soluble molecules and ions smaller
than 50 Daltons can enter the cell through aqueous-
filled channels; larger molecules and ions must enter
through a separate transport route.

14. DEGREE OF
INONIZATION
A drug's capacity to penetrate tissue is
significantly influenced by its level of
ionization. The ionization and diffusion
of drugs into cells are also influenced by
the ECF and blood pH.
Drugs that remain unionized at
these pH levels can enter cells
considerably more quickly.
Unless altered in situations like
systemic acidosis or alkalosis, the
blood and ECF pH, which is
typically constant at 7.4, have little
impact on drug diffusion.

15. pKa
pH of the Blood, CSF and ECF is 7.4
(constant)
Drug should penetrate the Cell membrane
in the form of a Unionized (Lipophilicity).
Weak acidic drug should unionize in strong
acidic environment
Weak basic drug should unionize in strong
basic environment
Both weak acidic/basic drug should ionize
in a Neutral environment

16. O/W partition Coefficient
K o/w - Ratio
between the Drug
distributed in both
the oil and water
phase
If K o/w value is
Positive – More
Lipophilic
(Unionised)
If K o/w value is
Negative – More
Hydrophilic
(Ionised)
O/W partition
Coefficient is
determined by using
Octanol Water as a
Solvent.

17. PHYSIOLOGICAL BARRIERS
Simple carrier endothelial barrier
Capillary supplies the Blood to the inner tissue
All drugs ionized or unionized drugs with a molecular size of 600
Dalton diffuse through the capillary endothelium to interstitial fluid.
Only drugs that are bound to that blood components can’t pass
through this barrier because of the larger size of the complex.

18. Simple Cell Membrane
Barrier
• Once the drug diffuses through the capillary to extracellular fluids, it’s
further entry into cells of most tissue is limited.
• Simple cell membrane is similar to the lipoidal barrier.
• Polar and Hydrophilic drugs will pass through it. (Passively)
• Lipophilic drugs with 50 – 600 Dalton molecular size will pass the
membrane.
• Hydrophilic drugs with ˂50 Dalton will pass the membrane

19. THANK YOU…