Pharmacokinetics

Question 1

What are the four basic parameters of pharmacokinetics?

Answer 1

Clearance, volume of distribution, bioavailability, half-life.

Question 2

What is exposure and how does this fit into the time-concentration graph?

Answer 2

Exposure is the area under the concentration-time curve (AUC) typical units mgh/L.

Question 3

Why is drug absorption not relevant for IV administration, but oral (po) is?

Answer 3

Because IV is injected straight into the bloodstream so it has 100% absorption, yet drugs administered by other roots undergo loss of drug before reaching the bloodstream where they are absorbed.

Question 4

Define bioavailability:

Answer 4

The fraction of dose reaching the systemic circulation.

Question 5

How is bioavailability calculated?

Answer 5

F= AUCpo/AUCiv x doseiv/dosepo. If the doses are the same then F= AUCpo/AUCiv.

Question 6

What is a limitation of bioavailability?

Answer 6

First pass effect is the loss of drug occuring before the drug reaches the systemic circulation.

Question 7

Describe distribution of the drug:

Answer 7

Processes involved in the delivery of the drug to the tissues via the arterial blood, in the transfer of the drug from the general circulation to tissues.

Question 8

What is the parameter of distribution?

Answer 8

Volume of distribution.

Question 9

How is volume distribution calculated?

Answer 9

V= amount of drug in the body/plasma drug concentration.

Question 10

What are some determinants of volume of distribution?

Answer 10

Body mass, tissue binding (increased volume), drug binding to plasma elements (decreased volume).

Question 11

Define the loading dose:

Answer 11

This is the first dose of drug treatment, and is required to achieve a target concentration rapidly. It is related (and depends on) volume distribution.

Question 12

How is the loading dose calculated?

Answer 12

LD (mg) = V (L) x target concentration (mg/L)

If the V and target concentration are known then it is possible to work out the loading dose for a drug.

Question 13

Define drug elimination:

Answer 13

Drug elimination is the irreversible removal of the drug from the body.

Question 14

What are the two processes by which drug elimination can occur?

Answer 14

1. Drug excretion- loss of drug in bile or urine for H2O soluble drugs.
2. Drug metabolism- conversion of the drug into another chemical species for lipid soluble drugs.

Question 15

What parameter defines drug elimination?

Answer 15

Clearance

Question 16

Define clearance (CL):

Answer 16

Volume of plasma cleared of drug per unit time (L/h), a constant.

Question 17

How can clearance be calculated?

Answer 17

Elimination rate (mg/h) = clearance (L/h) x concentration (mg/L)

CLtotal body= CLrenal + CLhepatic + CLother

CL=dose/AUC

Question 18

Define maintenance dose rate (MD):

Answer 18

This is the dose rate to achieve and maintain a target concentration. At steady state, dose rate in=rate of elimination.

Question 19

How can maintenance dose rate be calculated?

Answer 19

MD(mg/h)= CL(L/h) x target concentration(mg/L)

If CL and target concentration are known then it is possible to estimate the maintenance dose of a drug.

Question 20

Define half life (T1/2):

Answer 20

Time required for drug concentration to fall by a half, and depends (independently) on volume and clearance. Usually constant irrespective of drug concentration. The amount of drug in the body at any time is related to the number of half-lives from drug administration.

Question 21

What can half-life be used to estimate?

Answer 21

How much drug is left in the body and how long it will take to reach steady-state.

Question 22

How can half life be calculated?

Answer 22

T1/2= 0.7 V/CL

Question 23

How does half life relate to drug elimination?

Answer 23

After 1 half life, 50% of the drug will have been eliminated.
After 4 half lives, >90% of the drug will have been eliminated from the body.

Question 24

How can elimination time be calculated?

Answer 24

Time required= 4 x half life length

Question 25

What is accumulation and how does it occur?

Answer 25

With repeating dosing or an infusion a drug will accumulate in the body until input rate equals output rate. This steady state occurs when drug accumulation is complete and concentrations have plateaued.

Question 26

How can the time required to reach a steady-state be calculated?

Answer 26

This is related to half-life and accumulation is more than 90% complete after 4 half lives (4 x T1/2).

Mathmatically it never reaches steady state, but in reality it does.

Question 27

How can the time it takes to get to steady state be overcome?

Answer 27

Using a loading dose.