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ADME
Dr. Rahul Kunkulol
Asso. Professor
Dept. of pharmacology
RMC, Loni
 The process by which the drug reversibly
leaves the site of administration and is
distributed through out the tissues of...
Volume into which a drug appears
to distribute with a concentration
equal to its plasma concentration
Drugs appear to distribute in the body as if it
were a single compartment. The magnitude
of the drug’s distribution is giv...
 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...
aVolume of
distribution
(aVd)
Retention Examples
< 5 L Vascular
compartment
Heparin, Insulin,
Warrfarin
Aprox.15 L Extrace...
 Plasma proteins
 Cellular reservoir
 Fat as reservoir
 Transcellular fluids
 Bones
Reservoirs Details Example
Cellular
High affinity for tissue
proteins (lipoproteins or
nucleoproteins)
Skeletal muscles, h...
 Plasma consists of
› ~90% water,
› ~8% plasma proteins
› ~2% other organic or inorganic species.
 Many drugs bind to th...
 A drug that binds plasma protein diffuses
less efficiently, than a drug that doesn’t.
 Albumin provides most of the ava...
 Highly protein bound drugs low Vd
 Highly protein bound drugs are difficult to
remove by dialysis
 PPB is capacity lim...
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
17
Displacement Interactions Drug A Drug B
% DRUG BEFORE DISPLACEMENT
BOUND
FREE
99
1
90
10
% DRUG AFTER DISPLACEMENT
BOUN...
 Importance has been over emphasized.
Most interactions can be better explained
by other mechanisms
 Increased availabil...
• Blood brain barrier
• Blood CSF barrier
• Placental barrier
characteristics:
1. No pores in
endothelial membrane
2. Transporter in
endothelial cells
3. Glial cells surround
endotheli...
Distribution
 Extent depends on
 Blood flow
 Size, M.W. Of molecule
 Lipid solubility and ionization
 Plasma protein ...
Pharmacokinetics : Drug Distribution -Dr Rahul Kunkulol's Power point preparations
Pharmacokinetics : Drug Distribution -Dr Rahul Kunkulol's Power point preparations
Pharmacokinetics : Drug Distribution -Dr Rahul Kunkulol's Power point preparations
Pharmacokinetics : Drug Distribution -Dr Rahul Kunkulol's Power point preparations
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Pharmacokinetics : Drug Distribution -Dr Rahul Kunkulol's Power point preparations

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Dr Rahul Kunkulol's Power point preparations

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Pharmacokinetics : Drug Distribution -Dr Rahul Kunkulol's Power point preparations

  1. 1. ADME
  2. 2. Dr. Rahul Kunkulol Asso. Professor Dept. of pharmacology RMC, Loni
  3. 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. 4. Volume into which a drug appears to distribute with a concentration equal to its plasma concentration
  5. 5. 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
  6. 6.  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
  7. 7. 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
  8. 8.  Plasma proteins  Cellular reservoir  Fat as reservoir  Transcellular fluids  Bones
  9. 9. 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
  10. 10.  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.
  11. 11.  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
  12. 12.  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.
  13. 13. 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
  14. 14. 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%
  15. 15.  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
  16. 16. • Blood brain barrier • Blood CSF barrier • Placental barrier
  17. 17. 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
  18. 18. Distribution  Extent depends on  Blood flow  Size, M.W. Of molecule  Lipid solubility and ionization  Plasma protein binding  Tissue binding

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