Two Compartment Models

Question 1

the two compartment model is commonly used when the semi-log graph gives linear or non-linear kinetics

Answer 1

Non-linear or bi-exponential curves

Question 2

as it relates to the two compartment model what does the bi-exponential curve predict for IV administration

Answer 2

• that there are two distinct responses to the drug, a distribution and absorption phase

Question 3

In a 2 compartment model (IV bolus) the distributive phase is considered relatively slow, why?

Answer 3

• because although IV distributes rapidly to central compartment (Heart, liver, kidneys lungs) and hence Cp decrease rapidly the equilibrium or distribution to the peripheral compartment (tissues, fat, muscle) is very slow

Question 4

what is the rate of distribution determined by in the 2 compartment model

Answer 4

• the absolute magnitude of K12 to K21 i.e. how quickly the 2nd compartment compartment equlibrates
• the larger the difference, the more quickly equilibrium occurs

Question 5

when the distribution phase is long the equilibration between compartments is fast or slow

Answer 5

Slow

Question 6

Elimination occurs from both compartments? True False

Answer 6

False, only from central

Question 7

in the 2 compartment model elimination is considered to be the result of

Answer 7

biotransformation (metabolism) and excretion

Question 8

rate constants for the 2 compartment model are zero or first order kinetics

Answer 8

first order

Question 9

what are two terms commonly used to characterize how rapidly distrbution occurs in a 2 compartment model

Answer 9

shallow and deep

Question 10

A shallow compartment equilibrates (quickly or slowly) and has a (fast or short) distributive phase

Answer 10

A shallow compartment equlibrates rapidly and has a short distributive phase

Question 11

a deep compartment has a (long or short) distributive phase and equilibrates (slowly or quickly)

Answer 11

Long and slow

Question 12

what are the model parameters of the 2 compartment model obtained from A, B, alpha, beta

Answer 12

• K₂₁ (elimination rate constant from peripheral to central)
• K_el (elimination from central)
• k₁₂ (elimination from central to peripheral)

Question 13

how are A and B obtained

Answer 13

• from feathering a semilog plot
• the feathered line is the plot of the difference between actual data and data on the extrapolated line
  
  • the slope of the feathered line is -Ka/2.303

Question 14

How is AUC calculated for 2 compartment open model

Answer 14

AUC = A/alpha + B/beta

Question 15

what is beta half life

Answer 15

• biological half life of a drug
• time required for plasma concentration (Cp) to decline by 50% during post distributive phas or beta phase

Question 16

what is the half life in a 2 compartment model and how is it calculated

Answer 16

t_1/2 = 0.693/beta or beta half-life

Question 17

what is the alpha half-life (t1/2 alpha) a good measure of

Answer 17

it is an estimate of the duration of the alpha phase or distribution phase

Question 18

how many different volumes of distribution are there in a 2 comparment model, and what are they

Answer 18

• 4 different volumes
• Vdss = volume of distribution at steady state
• Vbeta = apparent volume of distribution during beta phase
• V1 and V2

Question 19

what is Vdss and what is it used for

Answer 19

• Volume of distribution at steady state
• used to relate Cp to Ab when drug concentration in both compartments is equal

Question 20

when is Vdss most appropriate to use

Answer 20

with IV infusions

Question 21

what is Vbeta

Answer 21

• apparent volume of distribution during Beta phase

Question 22

why is Vbeta also known as Vdarea?

Answer 22

• because it is calcutaled from the area under the Cp vs time curve

Question 23

Rate of absorption is calculated in a 2 compartment model using which model

Answer 23

Loo Riegelman

Question 24

AUC is proportional or disproportional to the drug reaching general circulation

Answer 24

proportional

Question 25

why is calculating the the amount absorbed more complex in the 2 compartment model

Answer 25

because the distribution phase overlaps with the absorption phase

Question 26

what may be used as simple indicators or absorption rate in bioavailability comparisons

Answer 26

• Tpk Time to peak plasma concentration AND
• Cpk time to peak plasma concentration