quantitative pharmacokinetics Flashcards
characteristics of a Compartment
-NOT a real anatomical region
-group of tissues w similar blood flow / drug affinity
-an open system (bc the drug can be eliminated from it)
-rapid mixing
-uniform distribution of drug within space
within a Compartment, the drug is _____ & _____
-uniformly distributed
-mixed rapidly & homogenously
what do rate constants represent in a Compartment
drug entry / exit from Compartment
what is 1CM
1-compartment model
what is 2CM
2-compartment model
factors of a 1CM
-single well-mixed container
-drug in blood is in rapid equilibrium w drug in extravascular tissues
-rapid mixing
-linear model- first order elimination
factors of a 2CM
-NO instantaneous distribution of drug within body
-has peripheral compartment
central compartment is comprised of _____
the vascular system (highly perfused tissues)
peripheral compartment is comprised of _____
poorly perfused tissues
the drug distributes to the peripheral compartment based on _____
the rate of transfer from the central compartment
what is zero-order kinetics
& example of drug(s)
a constant amount of drug is absorbed / eliminated per unit time
ethanol
what is an example of a zero-order process
a constant rate IV infusion
what is first-order kinetics
& example of drug(s)
a fraction of drug is absorbed / eliminated per unit time
most drugs
what is mixed-order kinetics
at low drug concentrations = first-order (dose-dependent)
at high drug concentrations = zero-order (dose-independent)
zero-order kinetics is dose-_____
independent
first-order kinetics is dose-_____
dependent
2 examples of drugs w mixed-order kinetics
phenytoin
&
salicylic acid (active metabolite of aspirin)
rate of change of amount of drug in the body is independent of _____
the quantity/concentration of drug in the body
why does drug concentration increase during the absorptive phase
bc rate of absorption is greater than rate of distribution / elimination
what happens at Cmax (drug concentration max)
rate of absorption falls
rate of distribution & elimination rises
-> and rate of absorption becomes = rate of elimination
what is peak concentration
the point where rate of absorption = rate of elimination
what is happening at stage 4 on the graph
there is a negative net balance & blood levels decline (bc very little drug is still available at the absorption site)
drug levels that fall into therapeutic window are considered _____
pharmacologically effective
what is true for drugs that fall in upper threshold of therapeutic window
they produce more side effects
what is the “duration of effect”
the time during which the drug concentration lies within the therapeutic window
what is true of the AUC (area under the curve) on the plasma-drug concentration time curve
AUC = the actual body exposure to the drug (mg/L x hr)
AUC is dependent on _____ AND _____
rate of elimination of drug from body
dose administered
AUC is directly proportional to _____ when _____
the dose, when drug follows linear kinetics
AUC is inversely proportional to _____
clearance of the drug
what is the elimination rate constant (k e)
a constant that links “rate of elimination” to available mass of drug in the body
equation for rate of elimination
rate of elim = mass x (k e)
mass: of drug in body
2 equations to find elim rate constant (k e)
(k e) = rate of elim / mass
(k e) = drug clearance / Vd
Vd: apparent volume of distribution
elim rate constant (k e) is a _____ per drug per patient
fixed value
what is the half life of a drug
the time it takes for plasma concentration of drug to decrease by 50%
(same amount of time per interval, and same fraction (50%) of drug eliminated, but amount of drug eliminated decreases)
half life equation
half life = 0.693 / (k e)
equation for “apparent volume of distribution” (Vd)
Vd = dose / Cp
Cp: drug concentration in blood
equation to find dose from blood concentration of drug
dose = Vd x Cp
Vd: apparent volume of distribution
Cp: drug concentration in blood
what shortens half life
decreased volume of distribution
increased clearance
what lengthens half life
increased volume of distribution
decreased clearance
strong plasma protein binding
what does not affect half life
dose administered
why do (oral dose) drug concentrations reach Cmax
(to get to Cmax)
rate of absorption > rate of elimination
(at Cmax)
rate of absorption = rate of elimination
what is steady state (in continuous IV infusion)
when rate of drug entry into the body is balanced by rate of elimination
&
no further drug accumulation occurs
equation that relates (R inf) and (C ss), and what is this equation independent of
(C ss) = (R inf) / clearance
(C ss): [drug] at steady state
(R inf): rate of infusion
*independent of # of compartments
why should an IV infusion have a loading dose
bc drugs w longer half-lives take longer to reach steady state
->
loading dose brings drug to therapeutic window quicker
what is a loading dose
an extra dose
equation for loading dose (drug has no absorption component)
loading dose = target Cp x Vd
target Cp: desired [plasma]
Vd: volume of distribution
bioavailability (F) of drug given by IV
= 1.0
equation for loading dose (drug HAS absorption component)
loading dose = target Cp x Vd/F
target Cp: desired [plasma]
Vd: volume of distribution
F: bioavailability
a drug w short half-life will reach Css _____ vs a drug w long half-life
quicker
as long as system is linear, increasing dose will _____ AUC
increase AUC
absolute oral bioavailability equation
absolute oral bioavailability = AUC oral / AUC iv
what is absolute bioavailability
the bioavailability when extravascular route is compared to IV route
what is relative bioavailability
% of test dosage that becomes bioavailable compared to reference dosage
what can relative bioavailability NOT tell you
how much drug test dosage delivers systemically (can only be determined when test dosage is compared to IV dose)
relative bioavailability for capsule equation (tablet vs capsule)
relative bioavailability for capsule (relative to tablet) = AUC capsule / AUC tablet
how many half-lives does it take to reach 93.8% of the target concentration
4
what is pharmacokinetic accumulation
during multi-dose regimen, when a drug has SLOW rate of elimination
equation for avg Css (concentration of drug at steady state)
Css avg = (F x D) / (Cl x t)
F: bioavailability
D: dose
Cl: clearance
t: dosing interval
independent of compartment #
Css avg units
mg/ml
time to reach steady state depends ONLY on _____
half-life
t (dose interval) if drug is given twice daily
12 hrs
t (dose interval) if drug is given 4x daily
6 hrs
increasing dosing rate will ONLY increase _____
avg steady state concentrations (does NOT shorten time taken to get to steady state)
in first-order kinetics, the rate of elimination (ROE) is directly proportional to _____
mass of the drug
which drugs should have a loading dose
drugs with the longest half-life
loading dose only changes _____, it does NOT change _____
changes time to get to therapeutic window
does NOT change time to get to steady state
the only factor that determines time to reach steady state
half-life
