Two Compartment Model

Question 1

How will the data of a drug that follows the 2CM appear on a graph of log Cp vs. time?

Answer 1

Curved, so can’t do 1CM analysis on this data

Question 2

Which organs are considered highly perfused?

Answer 2

• Adrenal
• Kidneys
• Thyroid
• Liver
• Heart
• Brain

Question 3

Which are organs are considered poorly perfused?

Answer 3

• Skin
• Muscle
• Connective tissue
• Fat

Question 4

What does K12 depict?

Answer 4

First-order constant going from central compartment to tissue compartment

Question 5

What does K21 depict?

Answer 5

First-order constant going from tissue compartment to central compartment

Question 6

What does K10 depict?

Answer 6

First-order constant leaving central comparmtent

Question 7

What is the difference between K0 and Ka?

Answer 7

• K0 depicts the first-order constant entering the central compartment for constant IV infusions
• Ka depicts the first-order constant entering the central compartment for oral, IM, and SC drugs

Question 8

Which rate constants are involved in the 2CM of an IV bolus?

Answer 8

K12, K21, and K10

Question 9

Which rate constants are involved in the 2CM of a constant IV infusion?

Answer 9

K12, K21, K10, and K0

Question 10

Which rate constants are involved in the 2CM of an oral, IM, or SC drug?

Answer 10

K12, K21, K10, and Ka

Question 11

What does K20 depict?

Answer 11

First-order constant for drug being eliminated from tissue compartment

Question 12

What are the 3 models of the 2 compartment open model for an IV bolus? Which rate constants are involved in each? Which model do we work w/?

Answer 12

1) Model A - K12, K21, and K10 (model we work w/)
2) Model B - K12, K21, and K20
3) Model C - K12, K21, K10, and K20

Question 13

What occurs during each phase of a log concentration vs. time graph for a 2CM drug?

Answer 13

• Phase 1 = drug enters central compartment and is filling it up
• Phase 2 = concentration rapidly dropping b/c central compartment is full and filling up peripheral compartment
• Phase 3 = eq’m between central and peripheral compartments
• Phase 4 = elimination has taken over and drug is being eliminated; elimination technically occurs in all phases but only significant during phase 4

Question 14

What is the relationship between tissue and plasma drug concentration for a 2CM?

Answer 14

• Plasma represents central compartment, so will be highest at Cp0 and will decrease as time increases
• Tissue will be 0 at Cp0 and will peak during phase 2 and decrease at same rate as plasma concentration as time increases

Question 15

Which equation explain distribution in the central compartment of a 2CM?

Answer 15

Cp = Dp / Vp

Question 16

Which equation explain distribution in the tissue compartment of a 2CM?

Answer 16

Ct = Dt / Vt

Question 17

What is b?

Answer 17

Depicts the rate of elimination (similar to k), so slope = -b/2.303 and t1/2 = 0.693/b

Question 18

What is the first step when doing calculation for 2CM?

Answer 18

Plot the points and use a ruler to see which points fall on a straight line

Question 19

How are b and B calculated?

Answer 19

• b is similar to k, so can use slope = -b/2.303 or t/12 = 0.693/b
• B similar to Cp0, so use y-int

Question 20

How are a and A calculated?

Answer 20

• a is the same as b, just for residual data

- A is the same as B, just for residual data instead of observed data

Question 21

Which formula would you use if you have Cp and B and you want to find b?

Answer 21

log Cp = -bt/2.303 + log B

Question 22

How do you calculate Cp’ extrapolated?

Answer 22

Using formula from the points you plotted to find b and B, plot in the time points to get Cp’ points

Question 23

How do you calculate residual points?

Answer 23

Cp minus Cp’

Question 24

How do you find Cp0 for a drug displaying 2CM?

Answer 24

A + B (must be larger than the largest data point)

Question 25

How can you calculate Vp (volume of distribution for central compartment)?

Answer 25

Vp = dose/Cp0, so Vp = dose/A+B or dose/K[AUC] infinity

Question 26

How can you calculate Vt (volume of distribution for tissue compartment)?

Answer 26

Vt = (Vp * k12) / k21

Question 27

What are the compartments in the 3 compartment open model?

Answer 27

Tissue compartment, central compartment, and deep tissue compartment (central goes to tissue and deep tissue)

Question 28

What determines the number of compartments or exponentials?

Answer 28

• Route of administration
• Rate of absorption
• Total time for sampling
• Number of samples during collection period
• Assay

Question 29

How can you tell how many compartments a log concentration vs. time curve represents?

Answer 29

• Straight line = 1 compartment
• Curved line w/ residual points forming a straight line = 2 compartments
• Curved line w/ residual points forming a curved line = over 2 compartments

Question 30

Which phase does the original data constitute and which data does the extrapolated data constitute?

Answer 30

• Original data = distribution phase

- Extrapolated data = elimination phase

Question 31

Why does total time of sampling affect the number of compartments?

Answer 31

Stopping too early or starting too late may cause you too miss the other compartments, so make sure to spread samples apart