Lecture 5

Question 1

PBK model development

Answer 1

1. model development
2. model verification
3. model application

Question 2

ADAM and m-ADAM models

Answer 2

multiple segements models. In m-ADAM there is a multilayer gut wall

Question 3

4 different sources of dose-nonlinearity

Answer 3

1. nonlinear metabolism
2. saturation of transporters
3. saturation of protein binding
4. solubility-limited absorption

Question 4

What is ASA

Answer 4

Automated sensitivity analysis = allows the assessment of changes in an outcome variable as a function of user-defined input variables

Question 5

What are the two methods of ASA and which is a one-at-a-time method?

Answer 5

Local sensitivity analysis (one-at-a-time)
Global sensitivity analysis

Question 6

What are assumptions of the VIVD model

Answer 6

1. metabolism is considered negligible
2. assumes monolayer cell culture in wells
3. size hepatocytes
4. assumes a hermetically sealed, cylindrical culture system
5. binding to cellular acidic phospholipids is assumed to be relevant for significantly ionised basic compounds

Question 7

What is VIVD model

Answer 7

virtual in vitro distribution

Question 8

Margin of exposure

Answer 8

NOAEL / predicted human exposure level

Question 9

What is the margin of exposure for compounds that are both genotoxic and carcinogenic?

Answer 9

10000 or higher