the two compartment model is commonly used when the semi-log graph gives linear or non-linear kinetics
Non-linear or bi-exponential curves
as it relates to the two compartment model what does the bi-exponential curve predict for IV administration
- that there are two distinct responses to the drug, a distribution and absorption phase
In a 2 compartment model (IV bolus) the distributive phase is considered relatively slow, why?
- because although IV distributes rapidly to central compartment (Heart, liver, kidneys lungs) and hence Cp decrease rapidly the equilibrium or distribution to the peripheral compartment (tissues, fat, muscle) is very slow
what is the rate of distribution determined by in the 2 compartment model
- the absolute magnitude of K12 to K21 i.e. how quickly the 2nd compartment compartment equlibrates
- the larger the difference, the more quickly equilibrium occurs
when the distribution phase is long the equilibration between compartments is fast or slow
Slow
Elimination occurs from both compartments? True False
False, only from central
in the 2 compartment model elimination is considered to be the result of
biotransformation (metabolism) and excretion
rate constants for the 2 compartment model are zero or first order kinetics
first order
what are two terms commonly used to characterize how rapidly distrbution occurs in a 2 compartment model
shallow and deep
A shallow compartment equilibrates (quickly or slowly) and has a (fast or short) distributive phase
A shallow compartment equlibrates rapidly and has a short distributive phase
a deep compartment has a (long or short) distributive phase and equilibrates (slowly or quickly)
Long and slow
what are the model parameters of the 2 compartment model obtained from A, B, alpha, beta
- K21 (elimination rate constant from peripheral to central)
- Kel (elimination from central)
- k12 (elimination from central to peripheral)
how are A and B obtained
- from feathering a semilog plot
- the feathered line is the plot of the difference between actual data and data on the extrapolated line
- the slope of the feathered line is -Ka/2.303
How is AUC calculated for 2 compartment open model
AUC = A/alpha + B/beta
what is beta half life
- biological half life of a drug
- time required for plasma concentration (Cp) to decline by 50% during post distributive phas or beta phase
what is the half life in a 2 compartment model and how is it calculated
t1/2 = 0.693/beta or beta half-life
what is the alpha half-life (t1/2 alpha) a good measure of
it is an estimate of the duration of the alpha phase or distribution phase
how many different volumes of distribution are there in a 2 comparment model, and what are they
- 4 different volumes
- Vdss = volume of distribution at steady state
- Vbeta = apparent volume of distribution during beta phase
- V1 and V2
what is Vdss and what is it used for
- Volume of distribution at steady state
- used to relate Cp to Ab when drug concentration in both compartments is equal
when is Vdss most appropriate to use
with IV infusions
what is Vbeta
- apparent volume of distribution during Beta phase
why is Vbeta also known as Vdarea?
- because it is calcutaled from the area under the Cp vs time curve
Rate of absorption is calculated in a 2 compartment model using which model
Loo Riegelman
AUC is proportional or disproportional to the drug reaching general circulation
proportional
