Multi-compartment Models

Question 1

when two or more decay phases are evident how many exponentials are required

Answer 1

3 or more hence 3 or more compartments

Question 2

how is the plasma concentration measured for Cp vs. time course in multicompartmental models

Answer 2

Cp = A e^{-_{alpha t}} + B e^{-beta t} + C e^{-gamma t}

Question 3

how is AUC calculated

Answer 3

AUC = A/alpha + B/Beta + C/gamma

Question 4

how many 3 compartment models are there

Answer 4

13

Question 5

what is the most commonly used multi-compartment model

Answer 5

one where oral and IV input are into the same compartment the central compartment which is in the middle

Question 6

linear multiple compartment models have

a) either second order and zero order input rate constants and zero order distribution and loss rate constants
b) either first order and zero order input rate constants and first order distribution and loss rate constants
c) either first order and zero order input rate constants and second order distribution and loss rate constants

Answer 6

b) either first order and zero order input rate constants and first order distribution and loss rate constants

Question 7

Rate constants are concentration dependent or independent in linear multi compartment models

Answer 7

independent

Question 8

what are drawbacks of compartment model approaches (2)

Answer 8

1. difficult to relate to physiology and actual pK in the body
   
   • difficult to evaluate changes in haemodynamics, enzyme fcn and protein binding on kinetics
   • hypothetical compartments don’t relate to tissues
2. difficult to assign specific compartment model uniquely describing a given set of data
   
   • determine based upon the number of exponential terms which makes the choice of model difficult

Question 9

How are physiological pk models developed

Answer 9

• experimental data is used to propose a model before concentration vs time data is available
• standard values of tissue mass and perfusion rate are obtained form literature

Question 10

flow models take these 6 things into account

Answer 10

1. the various organs of the body
2. blood flow to each organ
3. membrane permeability to the drug
4. protein binding
5. partition of drug between blood and tissue
6. mass of tissue

Question 11

what can flow models do that compartment models cannot

Answer 11

• distinguish between arterial and venous blood
• predict hemodynamic effects

Question 12

what is a primary assumption in flow models

Answer 12

that drug uptake by tissues is via perfusion rather than diffusion limited

Question 13

what is an advantages of physiological models over compartment models

Answer 13

• ability to more easily relate to physicological factors and predict haemodynamic effects in pk
  *

Question 14

What is extraction ration and how is extraction ratio calculated

Answer 14

• drug removal by an organ
• ER = Cl/Q
• where Q is blood from through the organ

Question 15

What is intrinsic clearance

Answer 15

• ability of the liver to remove drug in the absence of flow limitations
• a measure of enzyme activity, blood flow and blood drug binding
• typically measured for highly extracted drugs with flow dependent clearance

Question 16

What does the following equation measure and define each of the terms QH, fub and CLu int

CLH = QH[f_ub x CL_{u int}/QH + F_ub x CL_{u int}]

Answer 16

• CLH = total hepatic drug clearance
• QH = hepatic blood flow
• fub = free fraction of drug in blood
• CL_{u int} = intrinsic clearance of unbound drug

Question 17

Recirculatory Stochastic modesl are based on what principles

Answer 17

that the disposition or distribution of drug is the result of repetitive passes of druign in circulation

Question 18

what is an advantage of stochastic recirculatory model

Answer 18

• highlights the dangers of generalizing dimentionally limited models
• shows that total body clearance is not necessarily additive or equivalent to dose/AUC
  
  • only true if no pulmonary elim

Question 19

what is a model independent approach to pk

Answer 19

statistical moments approach

Question 20

How is AUMC Area under the firts moment curve calculated?

Answer 20

• Area under the first moment curve (AUMC) is calculated as the product of time and drug concentration vs. time
• AUMCinfinity = _{0 to infinity} tCpdt

Question 21

what is MRT, how is it calculated, and what is it a measure of

Answer 21

• mean residence time
• MRT = AUMC_infinty / AUC_infinity
• mean time for intact drug molecule to transit through the body

Question 22

what does MRT involve

Answer 22

a composite of all kinetic processes including in vivo release from the dosage form, absorption into teh body and all disposition processes

Question 23

What is MAT

Answer 23

• Mean Absorption Time
• the time when the adiminstred drug is not subject to disintegration or dissolution

Question 24

Which compartment model, 1, 2 or non-compartmental analysis are each of the three equations related to

• MAT = AUMC_infinity/AUC_infinity - 1/beta
• MAT = AUMC_infinity/AUC_infinity - [1/alpha + 1/beta - 1/k₂₁]
• MATuncorrected = AUMC_infinity/AUC_infinity - 1/beta

Answer 24

• 1 compartment model
  
  • MAT = AUMC_infinity/AUC_infinity - 1/beta
• 2 compartment model:
  
  • MAT = AUMC_infinity/AUC_infinity - [1/alpha + 1/beta - 1/k₂₁]
• Noncompartmental
  
  • MATuncorrected = AUMC_infinity/AUC_infinity - 1/beta