PKPD - NCA Flashcards
Regarding the mass balance principle, rate of change of drug in the body =
a) rate of absorption - rate of disposition
b) rate of absorption - rate of elimination
c) rate of disposition - rate of excretion
d) rate of disposition - rate of metabolism
B - rate of absorption - rate of elimination
B,B,D,C,D
Gentamicin has a volume of 18 L. Therefore, it is mostly distributed in
a) plasma only
b) plasma and interstitual fluid
c) plasma, interstitual fluid and intracellular water
d) plasma, interstitual fluid and intracellular water and bound to subcellular components
B - plasma and interstitual fluid
When a drug is administered through intravenous bolus injection,
a) the bioavailability value of the drug is between 0 and 100%
b) the drug is distributed throughout the body instantaneously
c) the drug may be subject to the first-pass effect when passing through the liver
d) the drug does NOT undergo absorption process
D - the drug does NOT undergo absorption process
When elimination of a drug follows the zero-order kinetics
a) the rate of elimination is associated with the amount of the drug in the body
b) the fraction eliminated per unit of time is a constant
c) a constant amount is being eliminated per unit of time
d) the relationship of drug concentration and time appears to be linear on semi-logarithmic scales
C - a constant amount is being eliminated per unit of time
Under linear kinetics, when the dose is increased, which of the following will stay the same?
a) the maximum drug concentration
b) the area under the curve (AUC) for time 0 to infinity
c) the absorption rate
d) the elimination half-life
D - the elimination half-life
AUC
area under plasma concentration-time curve
unit: amount*time/volume
AUMC
area under the moment curve
unit: amount*time^2/volume
(upside-down y)
lambda
unit: time ^-1
MRT
mean residence time
unit: time
MAT
mean absorption time
unit: time
D
dose
unit: amount or amount/kg body weight (BW)
Vss
volume of distribution at steady rate
unit: volume or volume/kg BW
CL
total clearance
unit: volume/time
k
elimination rate constant
unit: time^-1
ka
absorption rate constant
unit: time ^-1
t1/2
half-life
unit: time
fraction remaining or eliminated
no units
List two similarities between NCA and compartmental PK models
(1) both can be used to calculate important PK parameters, such as V, CL, t1/2, k, etc…
(2) we need to assume linear kinetics for both
List two main differences between NCA and compartmental PK models
(1) only can compartmental analysis characterize the relationship between drug concentration time
(2) NCA does not require the assumption of a specific compartmental model
Volume of distribution is the primary measure of _______. Total clearance is the primary measure of _________. AUC is the measure of ________.
drug distribution; drug elimination; drug exposure
AUMC has units in _____________.
amounttime^2/volume (or concentrationtime^2)
When dose is doubled, AUC should be _______ and AUMC should be________
doubled; doubled
Steps to calculate total AUC and AUMC
(1) calculate AUC (or AUMC) from time 0 to the time 1
(2) calculate AUC (or AUMC) from time 1 to time 2, from time 2 to time 3…from tlast2 to tlast
(3) a) calculate the lambda based on the last two time concentration-time points and b) use the lambda value to calculate AUC (or AUMC) from tlast to infinity
To improve the accuracy of estimation of PK parameters using NCA, we should ________
have sufficient number of plasma concentration-time points
MRT represents the time for _______ of an IV bolus dose to be eliminated
63.2%
If the dose increases, MRT should __________ (increase/decrease/stay the same)
stay the same
If AUC is doubled, MRT should __________ (doubled/ halved/ stay unchanged)
stay unchanged
Compare with the MRT value for the oral formulation of a drug, the MRT value of its IV formulation is always ________ (larger/smaller/unknown due to information)
smaller
When using NCA, the first-order elimination rate constant is calculated as _________ (lambda/the ratio of total AUC to total AUMC)
ratio of total AUC to total AUMC
The first-order absorption rate constant (ka) is calculated as the reciprocal of __________ (MRTni/MAT)
MAT
When V increases, MRT should ________
increase (MRT = 1/k; k = CL/V; MRT = V/CL. direct relationship between MRT and V)
When CL increases, t1/2 should _________
decrease (t1/2 = 0.693/k; k = CL/V; t1/2 = 0.693*V/CL. Inverse relationship between t1/2 and CL)
Greater k value indicates _______ (shorter/longer) MRT
shorter
