Volume of distribution (Vd) refers to the theoretical volume that a drug is distributed in the body. Vd is calculated as the dose administered divided by the drug concentration in plasma. A small Vd under 5L indicates distribution is mainly in plasma, while a large Vd over 41L means distribution is in tissues. Factors like molecular weight, pH, blood flow, and protein binding determine a drug's distribution. Drugs with high protein binding have a smaller Vd and longer duration since the bound fraction is unavailable for metabolism.

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2. Definition:
 reversible transfer of a drug between the blood &
the extra vascular fluids and tissues of the body.
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3. Sites of distribution :
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4. volume of distribution (Vd):
Theoretical volume that would have to be
available for drug to disperse
 the amount of fluid in which the administered
drug is distributed
Expressed as: in Liters
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5. Volume of distribution (VD)
 It is called as Apparent Volume because all parts
of the body equilibrated with the drug do not have
equal concentration
 Volume distribution of heparin 4L means?
It means heparin distributes about 4 liters of body fluid.
small volume of distribution?
1. Very large molecular weight.
2. Extensive plasma protein binding
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6. Volume distribution of Aminoglycosides is 14 liter means?
This drug has a low molecular weight but is hydrophilic.
It distribute into (plasma water + interstitial fluid) =extracellular fluid
(14 liters)
 ethanol has high volume of distribution
Ethanol has a low molecular weight and is hydrophobic
so can it move into the Plasma + Interistitium + cell
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7. Dose of the drug given (Q)
Vd = -----------------------------------------------------------
Concentration of drug in plasma (Cp)
So, if Dose given: 100mg &
Cp : 1mg/L {Cp is the plasma concentration }
Vd = Dose/ Cp
Vd = 100/1 = 100 L
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9. clinical signification
 determine the site of drug distribution
• total Vd < 5 L means that drug in plasma .
• Can removed by DIALYSIS
• vd > 41 drug in tissue . Cant removed by dialysis.
 calculation the total amount of drug in the body
from the equation (cp )
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10. clinical signification
 calculation of the loading dose needed to attain a
desired CP LD=Vd x CP
Calculation OF drug clearance
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11. THE DISTRIBUTION OF DRUG DEPENDS ON
 blood flow
Capillary permeability (BBB, placental barrier)
Drug factors (lipid solubility ionization _Molecular weight_ pKa of drug)
 Binding of drugs to macromolecules
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12. Blood flow
 The initial rate of distribution of a drug depends
heavily on blood flow to various organs
Brain, liver, kidney > muscle, skin > fat, bone
 the amount of drug in an organ is related to
mass of the organ and its properties, as well as to
the properties of the specific drug
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13. Molecular weight
 Low molecular weight drugs can cross easily
 High molecular weight drugs (albumin) can’t
cross the capillary membrane & remains in plasma
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14. pKa of drug & pH of media
 More dissociation….less crossing of membranes
 Blood is slightly alkaline (pH 7.4)
 Acidic low pKa drugs will be ionized more & less
crossing of membranes
Basic low pKa drugs will be ionized less & more
crossing of membranes
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15. Brain and CSF Penetration
 BBB is lipoidal and limits the entry of non-lipid soluble drugs
 Only lipid soluble unionized drugs penetrate and have action on the CNS
 inflammation of meanings of brain increases permeability of BBB
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16. Placental Transfer
Only lipid soluble Drugs can penetrate
limitation of hydrophillic drugs
Placental P-gp serves as limiting factor But its an
incomplete barrier
some influx transporters operate
 Thalidomide
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17. Plasma Protein Binding
 Free drug give the pharmacological effect
 Partially bounded
 Bounded to plasma protein ( ALBUMIN)
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18. The clinical significant implications of PPB are:
Highly PPB drugs are largely restricted to the vascular
compartment and have lower Vd.
The PPB fraction is not available for action
 The drugs with high physicochemical affinity for plasma proteins
(e.g. aspirin, sulfonamides) can replace the other drugs( e.g warfarin)
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19. Warfarin+ sulfonamide if given together?
If a sulfonamide is administered at same time, it will
displaces warfarin from albumin.
Leading to a rapid increase in the concentration of
free warfarin in plasma
This leads to Toxicity (bleeding)
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20. The clinical significant implications of PPB are:
High degree of protein binding makes the drug long acting,
because bound fraction is not available for metabolism
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Generally expressed plasma concentrations of the
drug refer to bound as well as free drug.
 In hypoalbuminemia, binding may be reduced and
high concentration of free drug may be attained
(e.g. phenytoin)
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