www.linkedin.com/in/dr-aboobecker-siddique-p-a-200783a0 PK is the quantitative study of drug movement in, through and out of the body During these processes the drug has to cross various biological membranes Absorption: Bio-Availability The fraction [F] of administered dose of a drug that reaches systemic circulation in the unchanged form’ I.V. –100% Bio-availablity Oral-Not 100%. WHY? Incompletely absorbed First pass metabolism i.m or s.c. also may be less than 100% -Local binding

1. PK is the quantitative study
of drug movement in,
through and out of the
body
During these processes the
drug has to cross various
biological membranes

2. PK-Membrane Transport
Mechanism by which drugs cross biological membrane

3. Membrane Transport…..
 Passive diffusion and Filtration
 Specialized transport
 Carrier transport
 Facilitated diffusion
 Active transport
 Pinocytosis

4. Passive diffusion
 Bidirectional process,
 Movement of molecules from
higher to lower conc [Down the gradient]
 Lipid soluble drugs- Passive diffusion, after
dissolving in the lipid of cell membrane
 Acidic drugs are unionized in acidic medium
 Alkaline drugs are unionized in alkaline Medium
 Unionized drugs are readily absorbed
 More lipid soluble » Diffuses quickly
 Greater the difference in concn gradient »
Quicker diffusion
•Ion trapping
•Urine alkalanized
in poisoning with
acidic drugs

5. Filtration

6. FILTRATION
Capillaries (Except in brain-Tight
junction) have large pores & most
drugs filter through these.
Lipid insoluble drugs cross
biological membranes by
filtration through these pores
Diffusion of drugs is dependent on
Rate of Blood Flow

7. Specialized transport: Carrier mediated
 Drug + CARRIER in the membrane → complex is
transported from one side of the membrane to other.
Eg. Calcium & iron absorption
 Carrier transport
1. Specific,
2. Saturable,
3. Competitively inhibited by - which utilize the same
carrier.

8. Specialized transport: Carrier mediated
Facilitated diffusion
 No energy required
• Drug + carrier[SLC Transporter] in the
membrane, → diffusion across the cell
membrane.
 Movement ONLY higher to lower conc
[ALONG].
Eg. Vit. B12 absorption

9. Specialized transport: Active transport
Movements of molecules – Low
conc. To high conc.
Against the conc.gradient
Require energy.
P-glycoprotein

10. Specialized transport: Active transport:Primary
Primary Active Transport
ATP Binding Cassette-
Transporter
Only out of the cytoplasm
Energy derived from ATP

11. Specialized transport: Active transport
:Secondary:
 Energy derived from movement of another
substance
 In the same direction-Symport
 In opp.direction -Antiport
 Pinocytosis; By formation of vesicles

12. Membrane Transport…..
Facilitated diffusion
Primary active
Secondary active- Symport
Secondary active-Antiport
Passive diffusion and Filtration
Specialized transport
 Carrier transport
 Facilitated diffusion
 Active transport
 Primary & Secondary
 Pinocytosis

13.  Absorption
 [Movement from site of administration to
circulation]
 ORAL:
 S.c, i.m: Absorbed by capillaries or lymphatics
 Topical: Lipid solubility-Hyoscine, Fentanyl, GTN,
Nicotine, Testosterone, Estradiol
 Cornea

14. BA=30/150
First pass metabolism

15. Absorption: Bio-Availability
 ‘The fraction [F] of administered dose of a drug that
reaches systemic circulation in the unchanged form’
 I.V. –100% Bio-availablity
 Oral-Not 100%. WHY?
1. Incompletely absorbed
2. First pass metabolism
 i.m or s.c. also may be less
than 100% -Local binding

16. Factors affecting rate of absorption
 Disintegration & dissolution time
 Formulation
 Particle size
 Concentration
 Lipid solubility
 pH & ionization
 Area & vascularity of the absorbing surface
 Gastrointestinal motility
 Presence of food
 Drugs
 Route of administration
 Diseases

17. Bioequivalence
 Comparison of bioavailability of different
formulations of the same drug
 Oral formulations containing same amount of
drug from different manufacturers may result
in different plasma conc
 Occur with poorly soluble, slowly absorbed
drugs due to differences in disintegration &
dissolution rates
 In drugs with low safety margin can result in
toxicity or therapeutic failure e.g. digoxin,
oral anticoagulants & corticosteroids

18. DISTRIBUTION
 ‘Reversible transfer of drugs between body fluid
compartments’
 Transport of drug to its site of action, storage
sites, metabolic sites & to the organs of excretion
 After absorption drug enters various body fluid
compartments.
 Plasma
 Interstitial fluid compartment
 Cellular fluid compartment.

19. Drug enters body
Plasma compartment:
•Large mol.wt.
•Bound to plasma proteins
•Cannot cross capillaries
•Remains trapped in vascular
compartment [4L]
Extracellular fluid:
•Low mol.wt.
•Hydrophilic
•Can cross capillaries(Slit junc)
•Can not enter cells(Cross
plasma membrane-Not lipid
soluble)
•Remains in
Plasma+InterstitiaL fluid[14L]
Total body water:
•Low mol.wt.
•Hydrophobic
•Can cross capillaries
•Can enter cells
(Cross plasma membrane)
•Distrbutes in vol. of 60% of
body wt.[42L]
Other sites:
•In pregnancy-Fetus
•Fat-Thiopental
Usually drugs not confined
One compt.

20. Distribution
 Determines efficacy, duration of action, mode of
metabolism & rate of excretion
 Involves filtration, diffusion & specialized transport
 Factors which determine: lipid solubility, ionization,
blood flow, presence of tissue specific transporters &
plasma protein binding

21. Volume of distribution
 Quantitative estimate of its tissue localization
 Vd= total amount of drug in body
concentration of drug in plasma

22. Volume of distribution…
 Vd is volume of fluid in which drug appears to be
distributed with a concentration equal to that of
plasma
 Small Vd → easily dialisable e.g. aspirin
 High Vd → e.g. pethidine cannot be dialysed
 Varies with
 Partition co-efficient - Protein binding
 Cardiac output - Membrane permeability,
 Tissue perfusion rate - Age
 Gender - Associated disease

23. V.D
 Factors affecting
1. Lipid solubility & Ionization-Lignocaine and
Heparin
2. Plasma protein binding
3. Tissue binding-Digoxin bound to heart,liver
4. Disease-CHF, Uremia
5. Fat:Lean body mass

24. Apparent volume of distribution
 aVD: “The volume that would accommodate all the drug in the
body, if the concn.throughout was the same as in plasma”
 Lipid insoluble: Small aVD-Eg.Gentamicin-.25L/kg
 Highly protein bound-Eg.Diclofenac-0.15L/kg.
 Highly tissue bound-Eg.Morphine-3.5L/kg
 High vol. of distribution-poisoning-difficult to remove by
dialysis

25. Redistribution
Highly lipid
soluble
Thiopentone-i.v
Distributed to
organs with high
blood flow.
Eg.Brain
site of
action
Unconcious
Less
vascular
areas
Eg.Fat,
muscle
Plasma
concn.falls
Concious
[Drug
withdraw
n from
brain]
Redistribution
10
Sec
10
Mts

27. Plasma protein binding
 Drug → ABSORPTION → Enters circulation
Binds to plasma proteins
[acidic to albumin, basic to a-acid
glycoprotein]
•Bound- inactive
•Temp. storage site,
•Long duration,
•Hemodialysis not
effective
Free
form-
Active

28. Plasma protein binding: Clinical Imp.A
Affects Vd
Delays metabolism, excretion,
Not available for action
Storage site

29. Tissue binding
 Delays excretion & prolongs duration of action
 E.g. lipid soluble drugs like thiopentone are bound
to adipose tissue
 Also acts as a reservoir
Tissue Binding drug
Adipose tissue thiopentone sodium
Muscles emetine
Bone tetracyclines
Retina chloroquine
Thyroid iodine

30. Blood brain
barrier
 Tight junctions of
brain capillaries + glial cells
enveloping capillaries
 Only lipid soluble, unionized drugs can cross this BBB
 More permeable to drugs during inflammation of
meninges
 Barrier is weak at CTZ, allows compounds to diffuse

31. Placental barrier
 Bet.mother and fetus
 Lipid soluble and unionized cross-anesthetics, alcohol
 High mol.wt.do not-insulin
 Teratogenicity ( Teratos = Monster)
 Tetracyclines, Thalidomide, Anti-cancer drugs, Sex
hormones