volume of distribution

Question 1

what is extent of distribution defined by?

Answer 1

apparent volume of distribution

Question 2

what is apparent volume of distribution based on?

Answer 2

the equilibrium concept assume there has been distribution between drug in tissue and drug in blood.
it relates to measured plasma drug con to the amount of drug within the body

Question 3

what is apparent volume of distribution (Vd)?

Answer 3

= amount of drug in the body at equilibirum
divided by
drug concentration in the plasma

Question 4

what is the range for volume of distribution?

Answer 4

• 3 to 40000L. 3 is the minimum as this is the volume of plasma.

Question 5

what does Vd NOT refer to?

Answer 5

physical volume it is an apparent volume

Question 6

what does the value depend on?

Answer 6

reference fluid it is measured in (blood, plasma, unbound drug)

Question 7

what is the volume and % body weight of extracellular water?

Answer 7

V= 13-16
BW%= 18-22

Question 8

what is the volume and % body weight of plasma?

Answer 8

v= 3L
BW%= 4

Question 9

what is the volume and % body weight of intersitial fluid?

Answer 9

V= 10-13L
BW%= 14-18

Question 10

what is the volume and % body weight of intracellular water?

Answer 10

V=25-28 L

BW%= 35-40

Question 11

what is the volume and % body weight of transcellular water?

Answer 11

V= 0.7-2L
BW%= 1-3

Question 12

what is the volume and % body weight of totalt body water/

Answer 12

v= 40-46
BW%= 55-65

Question 13

what affects the value of volume distribution?

Answer 13

 Drug can bind to plasma proteins, blood cells and tissue components!
 Acids (e.g., warfarin) show strong affinity for plasma proteins
 Basic drugs (e.g., fluoxetine) generally have higher V
 High affinity for acidic phospholipids in tissues
 Monoclonal antibodies – tend to reside in plasma

Question 14

what is subcellular distribution?

Answer 14

Implications:
 Prerequisite for therapeutic efficacy - antimalarials
 Reduced activity and off-target effects
 Vinblastine
 Azithromycin
 Safety issues – phospholipidosis

Question 15

what is needed for subcellular distribution in lysosomes?

Answer 15

 Sequester cationic amphiphilic drugs (LogP>2, pKa 6.5-11) (lungs, liver)
 Antibody drug conjugates

Question 16

which proteins do drugs bind to in plasam?

Answer 16

 ALBUMIN - acidic (e.g., warfarin) and neutral drugs (e.g., cyclosporine)
 1- ACID GLYCOPROTEIN - basic drugs
 GLOBULINS - steroids

Question 17

what is the extent of binding to plasma proteins?

Answer 17

fu = fraction of drug unbound in plasma (Cu/C)
1 – fu = fraction of drug bound
 fu is determined experimentally; it depends on:
 Affinity of the protein for the drug (Ka)
 Protein and drug concentration

Question 18

why is knowing fu of a drug so important?

Answer 18

 Total plasma concentration (C) is usually measured
 When fu is constant - changes in total plasma concentration reflect changes in the unbound drug concentration (C= Cu/fu)

Question 19

why is the unbound drug concentration important?

Answer 19

Assumption – only unbound drug diffuses into tissues in order to have pharmacological effect or to be eliminated