Clinical studies to measure pharmacokinetics

Question 1

Why is Pharmacokinetics important in drug development?

Answer 1

Enables us to find out how safe and efficacious a drug is.

They also help determine drug dose and dosing schedules.

Question 2

What is pharmacokinetics

Answer 2

the movement of drugs in the body.

Question 3

What is the importance of pre-clinical studies?

Answer 3

used to predict safety and efficacy of drugs in animal studies.

Question 4

What are the two disciplines of pre-clinical trials

Answer 4

Toxicology and general pharmacology

Question 5

Why are pharmacokinetic studies important?

Answer 5

ADME parameters
safety and efficacy
Helps to determine the half -life of a drug (prediction of drug safety profile)

Question 6

Why is plasma concentration important?

Answer 6

An important predictor of drug effect

Question 7

What are the key determinants of plasma concentration?

Answer 7

Absorption
Distribution
Metabolism
Excretion

Question 8

What is clearance?

Answer 8

metabolism and excretion

Question 9

Where can PK information be summarised?

Answer 9

Investigator brochure

Question 10

List the effects of PK on physiology (ADME):

Answer 10

GI tract (A,M)
Liver (M,E)
Kidneys (M,E)
Blood/Blood flow (D, protein binding)

Question 11

what is the effect of decreased kidney function on PK?

Answer 11

Decreased elimination and protein binding

Question 12

what is the effect of intestinal disease on PK?

Answer 12

Impaired absorption

Question 13

what is the effect of liver disease on PK?

Answer 13

decreased first pass metabolism and elimination.

fluid retention

Question 14

what is the effect of congestive heart failure?

Answer 14

decreased GI absorption and elimination.

altered volume of distribution

Question 15

what is the effect of ageing on PK?

Answer 15

decreased first pass metabolism, protein binding, hepatic and renal excretion.

Question 16

what does the rate and extent of distribution depend on?

Answer 16

Blood flow
active transport. diffusion
plasma protein binding (albumin) tissue binding
disease

Question 17

what is the distribution of plasma?

Answer 17

5% proportion of total body fluid.

Question 18

what is the distribution of interstitial fluid?

Answer 18

15%

Question 19

what is the distribution of intracellular fluid?

Answer 19

35%

Question 20

what is the distribution of intracellular fat?

Answer 20

20%

Question 21

What is the aim of drug metabolism?

Answer 21

to decrease drug activity.

to convert lipid soluble drugs into more polar water soluble metabolites to be excreted in bile or urine.

Question 22

where does drug metabolism take place

Answer 22

in the liver as phase 1 and 2 reactions

Question 23

what drug is an exception to liver metabolism?

Answer 23

codeine

Gut wall have enzymes that contribute to metabolism (CYP450)

Question 24

what is phase 1 metabolism?

Answer 24

converting molecules into simpler forms

Question 25

what is phase 2 metabolism?

Answer 25

conjugation, making molecules more water soluble.

Question 26

what enzymes are involved in metabolism phase 1?

Answer 26

monoamine oxidase | alcohol dehydrogenase

Question 27

what are the routes of excretion?

Answer 27

kidney Biliary sweat/breath/breastmilk

Question 28

what is renal excretion?

Answer 28

Glomerular filtration proximal tubule | proximal and distal tubules

Question 29

what is biliary excretion?

Answer 29

active transport/secretion e.g. Rifampicin | Into Bile and Faeces

Question 30

what are the parameters for plasma concentration?

Answer 30

Cmax = max conc. Tmax = time taken to reach max conc. t1/2 (half-life) = time taken for drug conc. to fall by 1/2 area under the curve

Question 31

what does the area under the curve signify?

Answer 31

the total amount of drug the system is exposed to for the entire time course

Question 32

what are the conceptual parameters?

Answer 32

clearance bioavailability volume of distribution

Question 33

what is bioavailability?

Answer 33

proportion of drugs reaching systemic circulation

Question 34

what are the factors influencing bioavailability

Answer 34

pharmaceutical preparation physiochemical interaction patient factos 1st pass metabolism

Question 35

What is the investigator brochure?

Answer 35

a comprehensive summary of the preclinical and clinical pharmacology data for the investigational medicinal product (for first in human trial, there will be no clinical data available).

Question 36

What is the investigational medicinal product dossier?

Answer 36

It contains information related to the quality, manufacture and control of the investigational medicinal product.