Lecture 3 - pharmacokinetic modelling

Question 1

What do pharmacokinetic models describe?

Answer 1

They are relatively simple mathematical schemes that represent complex physiological spces or processes

Question 2

What are the most commonly used pharmacokinetic models?

Answer 2

comparatmental models

Question 3

Why do we measure the plasma drug conecntration?

Answer 3

it provides us with useful information about how much drug is in the tissue, beacuse it is generally related to the plasma concentration

Question 4

What do we measure with the zero-order elimination model?

Answer 4

the plot of the log of the plasma concentration vs time, constant amount of drug is eliminated per unit time

Question 5

When can there be zero-order elimination?

Answer 5

when therapeutic doses of drugs exceed the capacity of elimination mechanisms

Question 6

What is first-order elimination?

Answer 6

it refers to the elimination of a constant fraction of drug per unit time

the rate of elimination is a linear function of the plasma drug concentration

Question 7

When does first order elimination occur?

Answer 7

when elimination systems are not saturated by the drugs

a constant fraction of drug is eliminated per unit ti,,e

Question 8

What is a one-compartment open model?

Answer 8

when the body is seen as one continous fluid phase into which the drug is administered and through which it diffuses

Question 9

What is meant by open model

Answer 9

open= continous loss of drugs from the compartment due to metabolism end excretion

the openness of the body causes drug molecules to disengage from receptors and so terminates drug action

Question 10

What formula can describe the drug concentration following a single IV administration

Answer 10

Question 11

What is elimination half life?

Answer 11

the time it takes for the plasma drug concentration to be reduced by 50%

Question 12

What drugs does the half life concept apply to?

Answer 12

only drugs that aare eliminated by first order kinetics

Question 13

how is half-life determined?

Answer 13

log plasma drug concentration

vs

time profile for drugs fitting a one-compartment model

or from the elimination phase for drugs fitting the two-compartment model

Question 14

what is the general rule for all doses in which first-order elimination occurs, in regards to half-life?

Answer 14

>95% of the drug will be eliminated in a time interval equal to five half-lives

Question 15

What is C₀

Answer 15

plasma concentratio at 0 time

Question 16

C_max?

Answer 16

peak plasma concentration following a single non-iv dose of drug

Question 17

T_max

Answer 17

time of peak plasma concnetration

Question 18

T_1/2el

Answer 18

half life of elimination

Question 19

AUC

Answer 19

area under the curve

under the plot of concentration of drug in plasma against time

represents the total amount of drug absorbed by the body, irrespective of the rate of absorption

Question 20

What is the two-compartment model used for?

Answer 20

distribution and elimination of drugs

Question 21

How does a two-compartmend model work?

Answer 21

initial rapid changes in the plasma concentration of a drug are observed beacuase of distribution phase, the time required for the drug to reach an equilibrium distribution between a central compartment, plasma space, and a second compartment such as aggregate tissues and fluids to which the drug distributes

Question 22

what is meant by two compartments being notational?

Answer 22

they do not bear a constant relationship to the familiar physiological compartments

Question 23

Characteristics of the central compartment?

Answer 23

allows rapid, more or less instantaenous equilibrium

blood, interstitial fluid and highly perfused organs - heart, liver, lungs and kidney

Question 24

what is the peripheral compartment

Answer 24

comes to equilibrium woth the central compartment more slowly

less well perfused organs - skin, bone, fat

Question 25

what is the noncompartmental PK analysis dependent upon?

Answer 25

estimation of total drug exposure

Question 26

How is total drug expose estiamted?

Answer 26

by the area under the curve methods, trapezoidal rule

Question 27

What is the trapezoidal rule?

Answer 27

divide the plasma concentration-time profile to several trapezoids and add the AUC of these trapezoids

Question 28

How is the concentration-time or curve described?

Answer 28

in term of sloped

heights

areas

moments

SHAM

Question 29

What can we calculate with the SHAM values?

Answer 29

respective disposition half lived

and

Vd area