Chapter 10 - Compartment Models Flashcards
what is a pharmacokinetic “compartment”
a group of tissues that are similar in certain characteristics (rate of blood flow, partition properties)
or specific entities - drug affinity, plasma proteins
a pharmacokinetic model is a_______ description of a biologic system which can be used to stimulate ________ that describe the movement of drugs in the body
mathematical description
rate processes
a pharmacokinetic model devlops mathematical equations which describe what?
the concentration of drug in the body
a pharmacokinetic model expresses a ______ relationship between various parameters
quantitative
a pharmacokinetic model predicts ___________ in the body as a function of _______
drug concentration in the body as a function of time
2 general factors to consider when compartment modeling
simplicity and validation
what is the simplest and most reasonable model
the 1 compartment model
true or false
the most complex model is proposed first
FALSE - the simplest and most reasonable (1 compartment)
in compartment modeling, we must have at least ____% accuracy
90%
the validation of compartment modeling is its goodness of fit between ____ and ____
experimental data and calculated values
the pharmacokinetics of MOST DRUGS is adequately described by what compartment model
ONE COMPARTMENT
if the proposed predicted 1 compartment model doesn’t appear adeqate, what is done next
the next complex model is proposed and tested
most drugs have ___ order in and ___ order out
first order
-by EV route, ___ almost always follows ___ order kinetics
-by constant IV infusion, the rate constant of drug input is _____
-by rapid IV bolus injection, the rate constant is _____
EV - Ka almost always follows 1st order kinetics (rate constant of absorption)
constant infusion - Ko (zero order rate of administration)
rapid IV bolus - NO RATE CONSTANT ASSOCIATED
“the removal of drug from the central compartment
drug output
for this discussion - only drug removed by kidneys
the elimination rate constant (___), almost always follows ___ order kinetics
Ke
1st order
define the central compartment
the compartment where the drug first appears in systemic circulation after the dose is given
typically describes the plasma + very well perfused tissues. the distribution between the plasma and these very well perfused tissues is basically instantaneous
what is “compartment #1”
the central compartmenr
as the kidney removes drug from the body, where is it being removed from
the central compartment
true or false
the minimum volume of the central compartment is 3L
TRUE
what is the peripheral tissue compartment
the SECOND compartment where the drug appears after it has already appeared in the central
compartment #2
a particular drug distributes into MORE THAN 1 tissue compartment
what is the peripheral tissue compartment called
the shallow tissue compartment
compartment #3 now comes into play – the deep tissue compartment
define the deep tissue compartment
compartment #3
the THIRD compartment where the drug may appear after it has appeared in the central compartment
K10 is known as a…..
transfer rate constant
true or false
IN A ONE COMPARTMENT MODEL, if the concentration of a drug decreases in the plasma due to elimination, the concentration also decreases in other tissues by the same factor
true
pharmacokinetic models are referred to as open or closed models? why
open models - bc the drug is removed by an excretion mechanism
closed model means that the drug is not removed by excretion and stays in the body forever - this obviously doesnt apply to our body. our body is an open system bc of the excretion mechanisms
true or false
not all pharmacokinetic models are open models
FALSE - they all are open
bc all drugs given are removed by some excretion mechanism
true or false
the half life of a drug is always constant
FALSE - ONLY if it follows 1st order kinetics - doesnt matter the route of administration, dosage form, or anything - always constant
true or false
distribution takes a long time so it takes a while for the plasma and the tissues to reach equilibrium
FALSE - almost instantaneous and equilibrium is reached immediately
their concentrations will thus be identical (between plasma and tissue)
blood and all other readily accessible fluids and tissues may generally be treated as a __ ___ ___ — the central compartment
common homogenous unit
true or false
if the Vd is 3L, we cannot necessarily conclude that there is no distribution
FALSE- we can conclude that there is no distribution into tissues. drug is only going into the 3L of plasma
true or false
in a ONE COMPARTMENT MODEL, if a change in drug concentration occurs in the plasma, there will be PROPORTIONAL concentration changes in the other tissues/fluids that comprise the central compartment
TRUE
not necessarily the exact same amount tho!! just a proportional change
true or false
the one compartment model assumes that the concentration of a drug in each fluid/tissue is the same at any given time
FALSE
drugs that exhibit MULTI-COMPARTMENT pharmacokinetic model do what?
distribute into different tissues at DIFFERENT RATES
as mentioned, drugs that follow a multi-compartment model distribute into different tissues at different rates
what is the general rule for this? which type of tissues reach equilibrium with plasma first? give examples
highly perfused tissues reach equilibrium faster than poorly perfused tissues
also, particular drugs are more bound to distribute more in specific tissues
highly lipid soluble drugs are prone to distribute more in adipose tissue. drugs that bind protein are bound to be concentrated in the plasma!!!!! bc when bound to protein - they can’t diffuse into tissues
true or false
drugs that bind proteins tend to be more concentrated in the tissues
FALSE - more concentrated in the plasma
bc there are proteins in the plasma and the drugs bind to them to form a complex
this complex cant diffuse into the tissues
tetracycline is an example of a drug that follows what compartment model
MULTI
bc accumulates into calcium containing tissues like teeth and bone
true or false
highly lipid soluble drugs and highly protein bound drugs follow the one compartment model
FALSE - multi
distribute into certain tissues more
in a one compartment model, what is the volume of distribution
the central compartment
what is the apparent volume of distribution in a multicompartment model
the sum of all the Vd’s of each compartment that the drug is distributed
explain what the 2 compartment model is
there is a central compartment + tissue compartment
the central compartment represents the plasma + the highly perfused tissues that it quickly reaches equilibrium with
the tissue compartment represents poorly perfused tissues and/or tissues that a specific drug concentrates in because of the drug’s affinity for it
everything is first order!
true or false
in the 2 compartment model, drug input and drug output are irreversible
true
what are K12, K21, and K10
K10 - first order rate constant. elimination from the central compartment
K12 - first order rate constant. transfer of drug FROM THE CENTRAL COMPARTMENT and to the tissue compartment
K21 - first order rate constant. transfer of drug from the tissue compartment and into the central compartment
what is the 3-compartment model
the 2 compartment model + a 3rd compartment that’s attached to either the central compartment of the tissue compartment
the 3rd compartment represents a deep tissue compartment - a POORLY PERFUSED tissue such as fat, OR represent drug binding to tissue protein
the pharmacokinetics of most drugs can be explained by fitting the data either to ___ or ____ model.
1 or 2
only some drugs have 3 compartment model kinetics
true or false
a drug distributes most rapidly to the central compartment, less rapidly to the 2nd compartment, and VERY SLOWLY to the 3rd compartment
true
name the 3 acceptable multicompartment models
why are there 3 different ones?
catenary (not universally used)
mammillary
perfusion
there are 3 diff ones bc the central compartment and the 2 tissue compartments may be represented in more than 1 configuration
this model consists of a series of compartments joined together like the compartments of a train
catenary model
NOT USED bc this isnt representative of our body — most functional organs are directly connected to the central compartment (plasma)
true or false
in the catenary multi-compartment model, a drug can go from the central compartment directly to the deep tissue
FALSE - CANNOT
has to go through shallow tissue first
in this multi-compartment model, every tissue is connected to the central compartment like satellites
mammillary model
true or false
in the mammillary model, there is NO TISSUE COMPARTMENT SANDWICHED between the central compartment and any tissue compartment
TRUE
all tissues are directly connected
FOR ALL MODELS - what does the central compartment represent
plasma + highly perfused tissues that rapidly reach equilibrium
true or false
in the mammillary model, each tissue compartment is INDEPENDENTLY connected to the central compartment
true
no compartment is sandwiched in between like in the catenary model
the multi-compartment model called the perfusion model also has what 2 names
the physiologic model/the blood flow model
the perfusion model is based on __________ data
known anatomic and physiologic data
drugs are carried to organs by ___ blood and leave by ____ blood
carried to organs by arterial blood and leave organs by venous blood
the perfusion/physiologic/blood flow model considers the fact that…..
(this is a major advantage of this model)
the drug is carried by BLOOD FLOW from the site of administration to various body organs
once it reaches these organs, it rapidly equilibrates with the interstitial fluid in the organ
in the perfusion model, what factors determine the concentration of drug in various tissues?
ALL OF THESE FACTORS CONTRIBUTE SIMULTANEOUSLY!!!!
-size of the organ tissue
-blood flow to the organ tissue
-ratios of drug conc between tissues and blood (experimentally determined)
how many compartments are there in the perfusion model?
varies with the drug!!!!!!
bc the only tissues that will be included are ones that have the presence of the drug or the drug penetrates them
what determines the number of compartments in the perfusion model
the specific drug and the specific organ tissues that it penetrates
which organs are generally NOT included in the perfusion model and why
the brain, bones, and other parts of the CNS
bc most drugs dont really penetrate here
