Week 5A Compartmental Model

Question 1

rapid distribution

Answer 1

to all tissues and rapid equilibrium between plasma and tissues
= 1-compartment

Question 2

initial distribution

Answer 2

in systemic circulation and surrounding tissues followed by slow distribution to all tissues
= 2-compartment

Question 3

why not one compartment?

Answer 3

• most drugs need time to distribute to the entire body
• tissues are perfused differently
• drug binds to tissues differently

Question 4

central and peripheral

what happens to drug at stages 1-4

Answer 4

1. central compartment that receives injection at t = 0
   II. distributing to peripheral tissues
   III peripheral compartment comes into pseudoequilibrium with
   central compartment. rate at which is going in and going out of
   central compartment is the same
   IV. drug is cleared through body. conc falls at log linear decay.

Question 5

alpha and beta

Answer 5

macroconstants 
hybrid first-order rate constants
fast distribution (α) phase and slow elimination (β) phase

Question 6

The drug concentration at any time after an i.v. bolus which follows a 2- compartment model is described by a

Answer 6

biexponential equation

Question 7

if plasma concentrations are obtained shortly after an iv bolus and a 1-compartment model is assumed

Answer 7

the drug half-life may be underestimated (and k overestimated)
wait 3-4 t1/2a’s to ensure completion of distribution phase if applying a 1-compartment model

Question 8

construct a line for the post-distribution (elimination) phase

Answer 8

and obtain the slope b and the y-intercept B

Question 9

calculate the difference (residual) at each time point between the actual value (w,x,y,z) on the original curve and

Answer 9

the extrapolated value (w’,x’,y’,z’) on the elimination line.

Question 10

Varea

Answer 10

V during elimination phase

very useful

Question 11

Vextrap

Answer 11

• this is the volume value calculated if the distribution phase is ignored by applying a one compartment model for a two compartment drug
• not very useful

Question 12

Vss

Answer 12

• total amount of drug in the body at ‘steady state’ with drug concentration in plasma
-reflects the relationship between a dose and the observe plasma concentrations once the tissue Reservoir fills
Vss x Ctarget&raquo_space; V1target

Question 13

relationship between all V’s

Answer 13

Vextrap > Varea > Vss > V1

For one compartment model, these values are equal, V

Question 14

Administration of higher doses results in

Answer 14

higher drug concentrations (proportional)

Question 15

Larger distribution rate constant leads to

Answer 15

more rapid completion of the distribution phase without effecting the elimination rate.

Question 16

Larger hybrid elimination rate constant

Answer 16

(higher total body clearance) results in faster rate of drug elimination.

Question 17

Changing the volume of distribution affects

Answer 17

all of the macroconstants as well as the microconstant k. When all else is held constant, large volumes of distribution give very long terminal half-lives.

Question 18

V1

Answer 18

Accounts for instantaneous equilibrium with tissue reservoir is empty
calculating LD with V1: undershoot therapeutic target, need to wait until MD reaches ss

Question 19

Two compartment drugs also have

Answer 19

slower distribution