Pharmacokinetics

2. OBJECTIVE
1. Define absorption.
2. Discuss different processes of transport
across cell membrane.
3. Define Fick’s Law.
4. Enumerate factors affecting drug absorption.
5. What is Hendersen Hesselbach equation?

3. ABSORPTION
Transport of Drugs
across Cell membrane
DR. MEHTAB MUNIR
Assistant Professor
Pharmacology
Federal Medical College

4. To obtain
 Right effect
 Of right intensity
 At right time
 For right duration
 With minimum toxicity

5. ABSORPTION
 It is the transfer of drug from site of
administration to the blood stream
 For intravenous route, Absorption is
complete

6. THE BASIC PROCESSES BY WHICH DRUG
PASSES THROUGH CELL MEMBRANE
 Passive diffusion
 Filtration
 Facilitated diffusion
 Active transport
 Pinocytosis

7. 1.PASSIVE DIFFUSION
 Main process by which most of the drugs are
absorbed
 Drug passes through cell membrane
from higher concentration to lower
concentration
 It depends upon
(a) Absorbing surface area
(b) Lipid solubility
(c) Concentration gradient

8. PASSIVE DIFFUSION (cont.)
It follows Fick's law, According to this law
* Greater the concentration gradient greater will be the
drug absorption
* Larger the surface area, greater will be the drug
absorption
* Thicker the medium, lesser will be the drug absorption
* Larger the molecule size, lesser will be the drug
absorption

9.  Fick's law:
Flux (molecules per unit time) =
Area x Permeability coefficient
(C1- C2) x ------------------------------------------
Thickness

11. 2. FILTERTATION
 Drugs pass through pores of membrane
by means of their hydrostatic or osmotic
pressure
 Water, ions and some low molecular
weight substances pass through the
pores

13. 3. FACILITATED DIFFUSION
 Drugs pass through cell membrane with the
help of carrier or transport proteins
 Drugs are transported along their concentration
gradient
 Selective for chemical structures of a drug i.e. carrier
transport only those drugs which have specific
molecular structure
 Does not require energy
 Only few endogenous substances like glucose and
amino acids are absorbed through this process

15. 4. ACTIVE TRANSPORT
 Specialized process in which drugs move
across the cell membrane with the help of
carrier or transport proteins
 Saturable process
 Works against the concentration gradient i.e.
from low to high concentration

16.  Selective for chemical structure of a drug
 Requires energy
 Only few drugs are absorbed by this process
 Renal tubules, choroids plexus and neuronal
membrane

18. 5. PINOCYTOSIS OR ENDOCYTOSIS
 Minor method by which drugs are
transported into the cells
 Cells engulf the drug by throwing
pseudopodia
 Sucrose reaches the cell by this process
 Unicellular micro-organisms take the
nutrients

20. FACTORS AFFECTING THE
DRUG ABSORPTION
(A) FACTORS RELATED TO THE DRUG
1. Physical state of the drug
2. Disintegration of the drug
3. Molecular size of the drug
4. Solubility of the drug
5. Ionization of the drug

21. (B) FACTORS RELATED TO THE RECIPIENT
1. Absorbing surface area
2. Functional integrity of the absorbing
surface
3. Vascularity of the absorbing surface
4. Time of drug administration
5. Co-administration of other drugs
6. PH of medium

22. pH of the medium and drug
ionization
 Unionized or undissociated forms of drug are
lipid soluble, less polar as they have no charge
 Ionized forms are polar and water soluble and
less absorbed
pH of medium plays important role in ionization of
the drug and affects the drug absorption

23.  Weak acids ionize less in acidic medium, so
are better absorbed and weak bases are
better absorbed in alkaline medium
 Conversely weak acids are ionized more in
alkaline medium and weak bases ionize more
in acidic medium, hence poorly absorbed
 pka is the pH at of medium at which both un-
dissociated and dissociated forms are equal
(50% of the drug is ionized)

24. The Henderson Hasselbach equation relates the ratio
of protonated and unprotonated weak acid or
weak base to the molecule of pKa and the pH of
medium as follows
(Protonated)
Log----------------------- =pKa - pH
(Unprotonated)
This equation applies to both acidic and basic drugs

25. Observation shows that lower the pH relative
to pKa, the greater will be fraction of the
drug in the protonated form because
uncharged form is more lipid soluble, more
of a weak acid will be in lipid soluble form at
acid pH, while more of a basic drug will be in
the lipid soluble form at alkaline pH