This document provides an overview of pharmacokinetics and drug absorption. It defines key terms like bioavailability, discusses factors that influence drug absorption like lipid solubility and ionization, and mechanisms of drug transport including passive diffusion. Specific topics covered include the first-pass effect, importance of drug and environmental pH on absorption, and how molecular weight impacts absorption. Measurement of areas under the curve is presented as a method for assessing bioavailability.

1. Pharmacokinetics
Dr. Jahid
MBBS, M.phil (Pharmacology)
Head of Pharmacology (MD-AUCMS)

2. Learning objectives
 Learning objectives
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Drug absorption and clinical implications (1 hour)
Drug transport processes
Discuss factors affecting drug absorption
Define and describe the following pharmacokinetic
parameters: bioavailability (absolute and relative), area
under the curve
Define and describe bioequivalence studies
Describe the principle of first-pass effect
Explain the physicochemical factors influencing the
absorption of drugs across biological membranes

3.  Pharmacokinetics:
 It is a branch of pharmacology
which deals withabsorption
body
distribution
metabolism
and excretion
drug

4. Drug absorption

5. •

6. •

8. Drug absorption
 It is the process of drug transport from site of
administration to systemic circulation by crossing
biological membrane.
 Why drugs should be transported?
In order to reach its receptor and produces biological
functions.

9. ABSORPTION OCCURS FOR THE FOLLOWING DRUG
ADMINISTRATION SITE
1. oral
1. sublingual (will avoid 1st pass metabolism, breakdown in
stomach and liver)
2. transdermal (e.g. contraceptive) (very slow absorption)
3. rectal (use when patient is vomiting)
4. intramuscular injection
5. subcutaneous injection (Slow absorption)
6. miscellaneous - inhalation, intranasal, eye, nose, ear
drops

10. Drug absorption
 If oral……from Stomach & Intestine to portal circulation
 If Per-rectal……from Rectum to systemic circulation
 If Intramuscular…..from muscles to systemic circulation…
 No
absorption is needed if given
Intravenously.

11. Drug absorption
So, for absorption, drug needs crossing of the cell
membrane.

12. Drug absorption

13. Drug absorption
 Cell membrane consists ofLipid bilayer with
Interspersed protein (islands of protein)

14. Drug absorption
• Lipid layers are mostly “tight junction”
 Only lipid soluble substances can diffuse through it…..
 Water soluble substances can’t cross through tight lipid
layer…..

15. Drug absorption

16. Drug transport processes
 Passive Transport
Simple diffusion (99%)
 Almost
 Specialized transport
• Active transport
• Facilited diffusion
• Endocytosis
• Exocytosis
all drugs are absorbed by simple diffusion
with exception of a few.

17. Drug transport processes
 Simple diffusion Movement of solute from
high to low conc.
 No carrier protein
 No energy required.
 Almost all drug follow this
Process.

18. Drug transport processes
 Simple diffusion occur by Here the ink is spreading by
moving to lower ink solute
concentration.
 Eventually all the water will
be evenly colored.

19. Practice:
1. Release of Adrenaline into
synapse
2. Responsible for absorption of
glucose from intestine
3. This process don’t require
energy and carrier protein.
4. Vitamin B12 absorbed by this
process.

20. Drug absorption
Simple diffusion occurs
in Passive aqueous diffusion
Through aqueous channel
For small molecules (150-200
MW)
 Passive lipid diffusion
 Only lipid soluble drugs can
cross by this process.

21. Passive acqueous diffusion by-
 Fick’s Law:
 Rate = (C1 - C2) x (A x Permeability Coefficient)
T
 So this equation quantify Moves from high to low conc.
C1: higher concentration
area.
C2: lower concentration.
 Drug absorption is faster from
organ with large surface area.
A: diffusion surface area.
 Moreover drug absorption
PC: Permeability Coefficient
better from organ with thin
T: Thickness of the membrane
membrane barrier (Lungs)

22. Lipid Diffusion
•
In the case of weak acids and weak bases the ability to move
from aqueous to lipid or vice versa varies with the pH of the
medium.
•
Henderson-Hasselbalch equation (can be use to predict
the effect of pH change on ABSORPTION):
Acid: pH = pKa + log [A-]/[HA]
Base: pH = pKa + log [B]/ [HB+]

23. Drug absorption
 Factors influencing drug absorption (Drug factors) or
Physiochemical factors:
 Lipid solubility of drug
 Nature of the drug
 pH of the media (Stomach & Intestine)
 pKa of the drug
 Molecular size of drug
 Disintegration & dissolution of drug

24. Lipid solubility of drug
 Drugs which are lipophilic easily cross membrane
 Drugs which are lipophobic/hydrophilic have problem
crossing membrane
 This is a major source of variation in drug diffusion or
absorption.

25. DEGREE OF IONIZATION (POLARITY)
 Only a non-ionized (non polar) drugs diffuses across
the membrane, hence this is an important factor .
 Non polar drugs are lipid soluble.
 Polar drugs are water soluble, they can’t absorb from
biological membrane.

26. DEGREE OF IONIZATION (POLARITY)
 Lipid soluble = Non-ionized molecules (NaCl)
 Hydrophilic = Ionized molecules. (Na+, Cl- ).
So,
The more Lipid Soluble of drug------more absorption
The more Water Soluble of drug-----less absorption

27. Drug absorption
MEMBRANE
Ionized Molecule
(water soluble)
CELL
Non-Ionized Molecule
(lipid soluble)

28. Effect of pH on Drug Absorption
 Acidic drug better absorbed in acidic media.
 Basic drug better absorbed in basic media.
Acidic drugs (Aspirin) are better absorbed in stomach
(in acidic media)
and
Basic drugs (Diazepum) are better absorbed in
intestine (in alkaline media)

29. Continue……….
Acidic drug better excreted in basic media.
Basic drug better excreted in acidic media
 Incase of acidic drug poisoning alkalization done to
promote excretion of that drug.
and
 Incase of basic drug poisoning acidification done to
promote excretion of that drug.

30. A. Diffusion of
non-ionized form of a weak acid through lipid membrane

31. Continue……….
B. Diffusion of non-ionized form of a weak base through lipid membrane.

32. Importance of environment pH &
drug pKa
 Degree of ionization (polarity) depends on the pKa of
drug (and pH of body fluid).
 pKa: value of drug pH when the concentration of
ionized and non-ionized drug form is equal.
 If pKa of a drug is equal to pH of the media, then…
“50% of the drug are ionized & 50% are non-ionized”

33. Acidic Drug
Acidic drugs – more NON ionized in acidic pH
N
pH 2
I
N
I
pH 6
N
I
pH 8
What’s the pKa for this drug?
= Non ionized molecules
= Ionized molecules
I
pH 9

34. TRY THIS OUT
Let’s consider the influence of pH on absorption of a
weak acid (pKa = 3.4) between gastric juice (pH1.4)
and plasma (pH7.4).
The mucosa can be considered a simple lipid barrier.

35. Where
Drug absorption more
drug???
Acid: pH = pKa + log [A-]/[HA]
Log [A-]/[HA] = (pH – pKa)
[A-]/[HA] = 10 (pH –pKa)
In plasma:
[A-]/[HA] = 10 (7.4-3.4) = 104 =10,000
In gastric juice:
[A-]/[HA] = 10 (1.4-3.4) = 10-2 = 0.01

36. MOLECULAR
Drug absorption
WEIGHT
 Molecular weight: this is relatively constant for most
drugs because molecular weights usually vary between
about 100 and 500.
Molecular size: The smaller in size-----more absorption

37. Drug absorption
Disintegration & dissolution of drug
Drug orally given
GIT
Disintegration (to form granules ) into small molecules
Dissolution into the aqueous media
Absorption

38. Drug absorption
 Host factors or Biological factors)
 Surface area
 Motility of GIT
 Presence of food (Drug binding)
 Blood supply at the absorptive area
 Destruction of drug in GIT

39. Drug absorption
Surface area
The more absorptive surface area, the more
absorption
Surface area of intestine is far greater than the SA of
stomach, so more drug absorption takes place in
Intestine
Relative SA:
Stomach 0.1 - 0.2
Small Intestine 100

40. Drug absorption
Motility of GIT
- Drugs are better absorbed in normal GIT movement
Blood supply at the absorptive area
- The more circulation
- the more maintenance of concentration gradient
- The more absorption

41. DRUG BINDING
 Binding on Food
 Increased
hydrochlorothiazide, propranolol
 Reduced
Ampicillin, isoniazid, rifampicin, erythromycin, thyroxine
Binding with other drug or compounds
Tetracycline with Ca2+
Chloroquine with retina

42. Drug absorption
 Destruction of drug in GIT
In GIT, there are gastric HCl, enzymes etc.
So, drugs may be destroyed in GIT before absorption
Example:
Benzyl penicillin is destroyed by gastric HCL
Insulin is destroyed by proteolytic enzymes

43. Drug Bio-availability
Bio: Blood ( Systemic
circulation)
Availability : How much
available?

44. Drug absorption
Simply….
 Bioavailability is the percentage of administered drug
available in the systemic circulation in respect of route
of administration.
If 100 mg of drug A is administered orally & 60 mg
reaches in systemic circulationthen the oral bioavailability of drug A is 60%

45. Drug absorption
Measurement of AUC

46. Drug absorption
 Factors influencing oral bioavailability of drug:
 Any route other than iv route
 Incomplete absorption of drug
Destruction of drug in GIT
 1st pass hepatic metabolism
Distribution of drug to other tissue.

47. Drug absorption
 Formula for bioavailability of drug:
 The systemic bioavailability of the drug F= f- (1-ER)
 Here: f = extent of absorption
Extraction Ratio (ER)= CLliver / Q
Q=where Q is hepatic blood flow, normally about 90 L/h.

48. 

Bioequivalence (BE): Definition
Two preparations of a drugs are consider Bioequivalence
when- there is absence of a significant difference in the rate
and extent of bioavailability at the same molar dose under
similar conditions in an appropriately designed study
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Importances:
Oral formulation of a drug from different company
Or different batches from same company may contain same
amount of drugs.

49. mL)
Concentration (ng/
90
80
70
60
Test/G eneric
50
Reference/B rand
40
30
20
10
0
0
5
10
15
Time (hours)
20
25
30

50. 1st pass hepatic metabolism
 After oral administration…..
Absorption from GIT
Portal circulation
Liver
Systemic circulation

51. 1st pass hepatic metabolism
Metabolism of drugs after absorption in the liver
while passing through it before reaching systemic
circulation….
This is known as 1st pass hepatic metabolism.

52. 1st pass hepatic metabolism
Usually most drugs undergo to some extent of 1st pass hepatic
metabolism
 But if this 1st pass hepatic metabolism happens extensively
for any drug, then the effect of that drug is not found by oral
administration
Example :
Nitroglycerine (GTN)