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.
2. Learning objectives
Learning objectives
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
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.
13. Drug absorption
Cell membrane consists ofLipid 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…..
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
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.
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
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%
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
Importances:
Oral formulation of a drug from different company
Or different batches from same company may contain same
amount of drugs.
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)