Pharmacokinetics (12 and 13)

Question 1

What is exposure?

Answer 1

Area under the concentration time curve typically uses units of mg.h/L

Question 2

What is the definition of bioavailability?

Answer 2

The fraction of dose reaching the systemic circulation

Question 3

How is bioavailability calculated?

Answer 3

(Area under curve for oral dose/area under curve for iv)*(dose iv/dose oral)

Question 4

What is the first pass effect?

Answer 4

Loss of drug occurring before the drug reaches the systemic circulation

Question 5

What is the volume distribution?

Answer 5

Amount of drug in the body/plasma drug concentration

Question 6

What are the determinants for volume of distribution?

Answer 6

Body mass (an increase in mass leads to an increase in volume of distribution)
Tissue binding (increases volume of distribution)
drug binding to plasma elements (decreases volume of distribution)

Question 7

What is a loading dose?

Answer 7

First dose of drug treatment which is required to rapidly achieve a target concentration

Question 8

How can the loading dose be calculated?

Answer 8

Loading Dose= Volume of distribution*target concentration

Question 9

What is drug elimination and what two process is it made of?

Answer 9

The irreversible removal of drug from the body, made of drug excretion (loss of drug in bile or urine) and drug metabolism (conversion of the drug into another chemical species)

Question 10

What parameter defines drug elimination?

Answer 10

Clearance

Question 11

What is clearance?

Answer 11

Volume of plasma cleared of drug per unit time units of L/h, this a constant value not dependant on drug concentration

Question 12

How is elimination rate calculated?

Answer 12

Elimination rate (mg/h)= clearance(L/h)*conc(mg/L)

Question 13

How is clearance calculated?

Answer 13

Dose/area under curve

Question 14

What is the maintenance dose rate and how is calculated?

Answer 14

The dose rate used to achieve and maintain a target concentration
MD=Clearance*target concentration
This value is typically then multiplied out so that it can be taken less frequently for convenience
Dose may need to to be corrected for bioavailability

Question 15

What is the definition of half life?

Answer 15

Time required for drug concentration to fall by half, dependant on volume and clearance and a constant value regardless of drug concentration

Question 16

How is the half life of a drug calculated?

Answer 16

Half life= 0.7*(Volume of distribution/clearance)

Question 17

What is the general rule about 4 half lives?

Answer 17

After 4 half-lives more than 90% of the drugs will be eliminated from the body so it can be assumed there is no therapeutic effect left
4 half lives is also regarded as the time required to reach steady state

Question 18

What is accumulation?

Answer 18

With repeated dosing or infusion drug will accumulate in the body until input rate= elimination rate, known as steady state where drug concentrations plateau

Question 19

What is the role of a loading dose in drug accumulation?

Answer 19

Use of a loading dose allows a target concentration/steady state to be reached faster