Dr Rahul Kunkulol's Power point preparations

1. ADME

2. Dr. Rahul Kunkulol
Asso. Professor
Dept. of pharmacology
RMC, Loni

3.  The process by which the drug reversibly
leaves the site of administration and is
distributed through out the tissues of the
body.
28 litres10 lit4 lit

4. Volume into which a drug appears
to distribute with a concentration
equal to its plasma concentration

6. Drugs appear to distribute in the body as if it
were a single compartment. The magnitude
of the drug’s distribution is given by the
apparent volume of distribution (Vd).
Vd = Amount of drug in body ÷ Conc. in Plasma
PRINCIPLE
(Apparent) Volume of Distribution:
Volume into which a drug appears to distribute
with a concentration equal to its plasma

8.  If drug does not cross capillary wall its Vd
is equal to plasma i.e. approx. 3L
 Drugs with high PP binding less Vd and
vice versa
 Vd more than body volume means
drugs are widely distributed

9. aVolume of
distribution
(aVd)
Retention Examples
< 5 L Vascular
compartment
Heparin, Insulin,
Warrfarin
Aprox.15 L Extracellular
compartment
Aspirin,
Tolbutamide
>20 L Throughout the body
Or
Penetration in various
tissues
Ethanol , Phenytoin,
Digoxin,
Phenobarb,
Morphine

10.  Plasma proteins
 Cellular reservoir
 Fat as reservoir
 Transcellular fluids
 Bones

11. Reservoirs Details Example
Cellular
High affinity for tissue
proteins (lipoproteins or
nucleoproteins)
Skeletal muscles, heart
Thyroid
Liver
Digoxin
Iodine
Chloroquine
Fats Highly lipid soluble drugs Thiopentone sodium
Transcellular Aqueous humor
Joint fluid
Chloramphenicol
Ampicillin
Bones - Tetracyclines , calcium

12.  Plasma consists of
› ~90% water,
› ~8% plasma proteins
› ~2% other organic or inorganic species.
 Many drugs bind to the plasma proteins as
they have low water solubility.
 Plasma protein binding limits distribution.

13.  A drug that binds plasma protein diffuses
less efficiently, than a drug that doesn’t.
 Albumin provides most of the available
‘sites’ for absorption, particularly of
acidic drugs.
› Warrfarin, Sulphonamides, Penicillins
 -globulin and an acid glycoprotein can
can become important in binding basic
drugs.
› Quinine, Imipramine, Lidocaine

14.  Highly protein bound drugs low Vd
 Highly protein bound drugs are difficult to
remove by dialysis
 PPB is capacity limited and saturable process.
› Example: Liver diseases, ureaemia
:Hypoalbuminemia--therapeutic dose may
become toxic
 More than one drug can bind to the same
site on albumin and can lead to
displacement interactions.

15. Plasma Tissue
Drug A
protein bound
Drug A
free
Drug A
free
Drug B
Drugs A and B both bind to the same plasma
protein

16. 17
Displacement Interactions Drug A Drug B
% DRUG BEFORE DISPLACEMENT
BOUND
FREE
99
1
90
10
% DRUG AFTER DISPLACEMENT
BOUND
FREE
98
2
89
11
% INCREASE IN FREE DRUG
CONCENTRATION
100 10
Interaction is significant if drug bind more than 95%

17.  Importance has been over emphasized.
Most interactions can be better explained
by other mechanisms
 Increased availability of free drug which is
displaced from plasma proteins, but
compensatory mechanisms maintain free
drug concentration
 Only important in interpretation of total
drug concentrations e.g. phenytoin / VPA

18. • Blood brain barrier
• Blood CSF barrier
• Placental barrier

19. characteristics:
1. No pores in
endothelial membrane
2. Transporter in
endothelial cells
3. Glial cells surround
endothelial cells
4. Less protein
concentration in
interstitial fluid

22. Distribution
 Extent depends on
 Blood flow
 Size, M.W. Of molecule
 Lipid solubility and ionization
 Plasma protein binding
 Tissue binding