ADME

Question 1

Definition of Pharmacokinetics

Answer 1

What the body does to the drug

- relationship between dosage and plasma levels

Question 2

Definition of Pharmacodynamics

Answer 2

What the drug does to the body

- relationship between plasma levels and therapeutic effects

Question 3

Why do we use plasma concentrations instead of tissue concentration?

Answer 3

Tissue concentration is very difficult to obtain from a live patient, and not pleasant. plasma can easily be measured

Question 4

Relationship between pharmacokinetics and pharmacodynamics?

Answer 4

A dosage/regimen is designed to reach a particular plasma concentration (PK), which is needed to produce a particular response in the patient (PD)

Question 5

Importance of pharmacokinetics?

Answer 5

to know the extent of distribution of the drug across tissues, to see the degree of the response produced

Question 6

What is ADME?

Answer 6

Absorption
Distribution
Metabolism
Elimination

Question 7

ADME model?

Answer 7

Drug dose absorbed into the blood (systemic circulation), then reaches target tissues. Drug lost from the blood by metabolism and elimination at the same time.

Question 8

The purpose of metabolism of drugs?

Answer 8

Change the structure of the molecule so that it can be excreted more easily in bile/kidneys. some drugs are eliminated unchanged

Question 9

Definition of absorption?

Answer 9

All processes from the site of administration to the site of measurement

Question 10

Definition of bioavailability?

Answer 10

a measure of the extent of absorption of unchanged administered compound

Question 11

Definition of distribution?

Answer 11

Reversible transfer of substance between site of measurement and other sites within the body

Question 12

Definition of metabolism?

Answer 12

irreversible loss of unchanged substance by chemical conversion

Question 13

Definition of excretion?

Answer 13

Irreversible loss of unchanged substance

Question 14

Definition of elimination?

Answer 14

Irreversible loss of unchanged substance from site of measurement

Question 15

What is pharmacokinetics a function of?

Answer 15

• physicochemical and structural properties of the drug
• dosage form
• route of administration
• physiology of the body

Question 16

Result of poor pharmacokinetic properties of a drug?

Answer 16

limited clinical application - as not taken up correctly

Question 17

What physiological factors can impact pharmacokinetics?

Answer 17

genetics, size, age, disease, co-administration, environmental factors e.g. smoking - affect on transporters etc

Question 18

What are the components of pharmacokinetics?

Answer 18

data: used to describe PK processes (e.g. plasma conc/time data, or deerived e.g. cumulative amount excreted)
models

Question 19

Types of PK models used for ADME processes?

Answer 19

1. Single equation: C = CoE(-KT) or differential
   rate constant - used to calculate drug conc at a given time
2. Kinetic compartmental models - data driven, used for fitting sparse clinical data (all individuals data fitted together to get an idea of PK). empirical - used to describe the data
3. PBPK models (physiologically based) - major tool for predicting in vivo PK from in vitro data

Question 20

What is the one compartment kinetic compartment model?

Answer 20

drug enters and absorbed –> drug in central compartment (blood) –> elimination

Question 21

What is the two compartment kinetic compartment model?

Answer 21

drug enters and absorbed –> drug in central compartment (blood) –> elimination

from central compartment - reversibly enters peripheral compartment via distribution (must be supported by data)

Question 22

Single compartment model of drug absorption and elimination?

Answer 22

Drug at absorption site -> drug in body -> then excreted OR metabolised -> metabolite in body -> eliminated metabolite

Question 23

Equation relating dose and pharmacokinetics?

Answer 23

dose = amount at absorption site + amount in body + amount excreted + amount metabolised

Question 24

Equation showing rate of change of drug in body?

Answer 24

rate of absorption - (rate of excretion + rate of metabolism)

Question 25

What is the therapeutic window?

Answer 25

the plasma concentration window at which the drug has a therapeutic effect

Question 26

Determinants of efficacy and toxicity of a drug?

Answer 26

Exposure: permeability and transport, metabolism, route of administration
Intrinsic biological effects (wanted and unwanted)
Elimination: metabolism and excretion by liver and kidneys etc

Question 27

PBPK modelling: physiological/system parameters considered?

Answer 27

tissue volumes and blood flow, tissue composition, intestinal pH, transit times, emzyme and transporter abundance

Question 28

PBPK modelling: population and external factors considered?

Answer 28

age, gender, race, disease status, genetic status, smoking, diet

Question 29

PBPK modelling: Drug dependent parameters to consider?

Answer 29

LogP, pKa, molecular weight, permeability, solubility, particle size, Clearance

Question 30

Benefits of PBPK modelling?

Answer 30

allows simulation of drug plasma and tissue concentration time profiles after iv and oral administration

Question 31

Role of PBPK modelling in pharma?

Answer 31

early development: ‘learn and confirm’, simulate the profile then use the clinical data to verify
late development: confidence that the model can predict profiles, for special populations e.g. paeds - can guide clinical studies

Question 32

Definition of disposition?

Answer 32

Elimination and distribution