Lecture 3 - pharmacokinetic modelling Flashcards
What do pharmacokinetic models describe?
They are relatively simple mathematical schemes that represent complex physiological spces or processes
What are the most commonly used pharmacokinetic models?
comparatmental models
Why do we measure the plasma drug conecntration?
it provides us with useful information about how much drug is in the tissue, beacuse it is generally related to the plasma concentration
What do we measure with the zero-order elimination model?
the plot of the log of the plasma concentration vs time, constant amount of drug is eliminated per unit time
When can there be zero-order elimination?
when therapeutic doses of drugs exceed the capacity of elimination mechanisms
What is first-order elimination?
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
When does first order elimination occur?
when elimination systems are not saturated by the drugs
a constant fraction of drug is eliminated per unit ti,,e
What is a one-compartment open model?
when the body is seen as one continous fluid phase into which the drug is administered and through which it diffuses
What is meant by open model
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
What formula can describe the drug concentration following a single IV administration
What is elimination half life?
the time it takes for the plasma drug concentration to be reduced by 50%
What drugs does the half life concept apply to?
only drugs that aare eliminated by first order kinetics
how is half-life determined?
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
what is the general rule for all doses in which first-order elimination occurs, in regards to half-life?
>95% of the drug will be eliminated in a time interval equal to five half-lives
What is C0
plasma concentratio at 0 time
Cmax?
peak plasma concentration following a single non-iv dose of drug
Tmax
time of peak plasma concnetration
T1/2el
half life of elimination
AUC
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
What is the two-compartment model used for?
distribution and elimination of drugs
How does a two-compartmend model work?
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
what is meant by two compartments being notational?
they do not bear a constant relationship to the familiar physiological compartments
Characteristics of the central compartment?
allows rapid, more or less instantaenous equilibrium
blood, interstitial fluid and highly perfused organs - heart, liver, lungs and kidney
what is the peripheral compartment
comes to equilibrium woth the central compartment more slowly
less well perfused organs - skin, bone, fat
