pharmacokinetics

1. Pharmacokinetics
Dr. Vishaal Bhat
Assistant Professor
Pharmacology
MMMC Manipal

2. What the body does to
the drug

3. Xenobiotic
 A compound to which the body
is exposed that is foreign to
the body.
 Includes drugs, industrial and
environmental chemicals

4. Routes of drug administration
Oral
Sublingual
Rectal
Transnasal
Intra-tracheal
Inhalational
Transdermal
Subcutaneous
Intramuscular
Intravenous

5. Routes of Administration

6. Pharmacokinetics
 Absorption
 Distribution
 Metabolism
 Excretion

7. ABSORPTION
 Describes the rate and extent to
which a drug leaves its site of
administration

8.  Absorption –the process by which
the drug moves into the body from
external source

9. Characteristics of a drug
favoring absorption
 Low molecular size
 Nonpolar
 Uncharged
 High lipid solubility

11. Mechanisms of solute transport
across membranes
 Passive diffusion
 Facilitated diffusion
 Active transport
 Endocytosis

12. Passive Diffusion
 Concentration gradient
 Lipid-water partition coefficient
 Area, Thickness and Permeability
of the membrane
 Ionic, pH, charge gradient*

13. Ionic Transport
 pH gradient
 Drug’s acid dissociation constant
(pKa)

14. pKa – pH value at which one half
of the drug is present in ionic
form
pKa = pH + log (HA)
(A-)

15. Drugs and ionisation
Theory
The more acidic the pH for an acidic
drug the more of it is unionised, and
vice versa for a basic drug
The Unionised fraction is lipid soluble
and thus crosses cell membranes
more easily than the Ionised fraction

16. Drugs and ionisation: Which of the
following statements are correct?
1. Ionised drugs do not easily cross lipid
barriers such as the gut, placenta and
blood brain
2. Acidic drugs are well absorbed in the
acidic medium of the stomach, basic
drugs in the alkaline medium of the
small bowel

17. Factors Affecting GI Absorption
 Gastric Emptying Time
 Intestinal Motility
 Food
 Formulation Factors
“First Pass Effect”

18. First Pass Metabolism
 Bioavailability: the fraction of the administered
dose reaching the systemic circulation
Dose
Destroyed
in gut
Not
absorbed
Destroyed
by gut wall
Destroyed
by liver
to
systemic
circulation

19. Bioavailability
Quantity of drug in systemic
circulation
Quantity of drug administered

20. Bioavailability
The liver (and gut wall) removes drugs
by ‘first pass’ metabolism and binding
so only a proportion reaches the
hepatic veins and the systemic
circulation

21. Distribution
 The movement of drug from the
blood to and from the tissues

22. Factors Affecting Drug
Distribution
 Affecting Rate of Distribution
Membrane Permeability
Blood Perfusion
 Affecting extent of distribution
Extent of plasma protein binding
Regional differences in pH
Lipid solubility
Available transport mechanisms
Intracellular Binding

23. Biotransformation
Chemical alteration of the drug in
the living organism so as to eliminate
it from the body.

24. Liver
 GI tract
 Kidney
 Lungs
 Blood
 Skin
 Placenta
Biotransformation

25. Metabolism
 Active Drug Inactive metabolite
 Active Drug Active or toxic
metabolite
 Inactive Prodrug Active drug
 Unexcretable drug Excretable
metabolite

26. Drug Metabolism
 Side effects are results that are different
from the primary, or therapeutic, effect, for
which a drug is taken.
 First-pass metabolism drug-metabolizing
enzymes in either the cells of the GI tract
or the liver can markedly reduce the
amount of drug that reaches the
bloodstream.

27. Biotransformation
 Phase I
 Phase II

28. PHASE I
Modify the chemical structure of a
drug
OXIDATION
REDUCTION
HYDROLYSIS

29. PHASE II
Conjugate a drug to large polar
molecules to :
Inactivate a drug
Enhance drug’s solubility
Enhance excretion rate

30. Conjugation reactions
 Glucoronidation – Acetaminophen,
Morphine,
 Sulfation – Acetaminophen,
Steroids
 Acetylation – Sulfonamides, INH,
Clonazepam

31. Drug Excretion
Removal of the drug and its
metabolites from the body

32. Organs Involved
 Kidney – Glomerular Filtration,
active tubular secretion and
passive tubular reabsorption.
 Lungs
 Faeces
 Bile
 Skin, Saliva, Milk.

33. Half life is the time taken
for the concentration (in the
plasma) to fall by one half
Plasma Half-life (t½)

34. HALF LIFE AND PERCENT OF DRUG
REMOVED (wash out)
Number of Percent of Drug Percent of Drug
Half-lives Remaining Removed
0 100 0
1 50 50
2 25 75
3 12.5 87.5
4 6.25 93.75
5 3.125 96.875

35. Zero order
kinetics:
• a fixed
amount of the
drug is
metabolised
in unit time
(e.g. alcohol)
First order
kinetics:
• a fixed
fraction of the
drug is
metabolised
in unit time
Zero-Order and
First order Kinetics

36. ADME - Summary