PharmacoKINETICS Flashcards
Define PharmacoKINTETICS…
What the animal does to the drug
Rate=
How fast the mass (dose) of a RX changes per unit time (mg/min)
Extent=
How much the mass (dose) of a RX changes in total
PharmacoKINETICS allows us to evaluate the rate and extend of…..
Absorption
Distribution
Elimination
Non-compartmental (stochastic) models
Most common in vet med.
statistical moments – like the Mean Residence Time (which basically represents the average amount of time any given molecule of drug stays in the body).
________: This system estimates pharmacokinetics by looking at populations
Population pharmacokinetics
_______: This uses pharmacokinetic data in multiple species to try to predict the behavior of a drug in a species for which this information is unknown.
Allometric scaling / Interspecies Extrapolation
Non-linear models
Used when drugs follow zero-order kinetics
the fraction of the given dose which finds its way into systemic circulation. This is calculated from the area under the plasma concentration-time curve (AUC)
Bioavailability (F)
Comparing 2 formulations of the same RX. Trade name VS generic
Bioequivalence
CMAX (maximum plasma concentration) and TMAX (the time at which CMAX is reached
Bioequivalence
Half-life (t1/2):
time required for the drug concentration to decrease by one-half (or 50%).
amount of drug eliminated per unit time is fixed, regardless of plasma concentration. There are relatively few drugs used in veterinary medicine that normally follow this.
Zero-order elimination/kinetics
The proportion of drug eliminated per unit time is fixed. The vast majority (maybe 95%) of drugs used in veterinary medicine will follow this type of kinetics at therapeutic doses, and for these drugs the compartment or stochastic models work well for predicting pharmacokinetics
First-order elimination/kinetics
Drugs that normally undergo first-order elimination may convert to zero-order if a _______ dose is given and elimination systems are saturated.
Massive/over
When saturation occurs the clearance (CLB) decreases and the half-life (t1/2) increases which can lead to…
RX accumulations AND potential toxicity
After 1 half-life ___% of the drug is gone
50%
After 2 half-lives ___% of the drug is gone
75%
After 3.3 half-lives ~___% of the drug will be gone
~90%
After 5 half-lives ~___% of the drug will be gone
~97%
What if we administered 2x normal dose to a food animal. Would we decrease holding time? Increase holding time? No change, and release animal at normal dose holding time?
We would INCREASE holding time by 1-HALF LIFE
V/D stands for…
Volume of Distribution
_____: the volume of a RX that would occupy if it was evenly distributed at the same concentration as in plasma (L/kg)
V/D
CL B stands for…
Clearance from body
_______: volume cleaned of the RX per unit time from the body
CL B
Plasma Concentration at Steady State (CpSS)
is the concentration at which the amount of drug going in (repeated dosing or CRI) is equal to the amount going out (clearance CLB)
If the dosing is continuous (CRI) plotting the plasma concentration over time would give a
Smooth curve
intermittent dosing (SID, BID, TID) will give you a
Sawtooth pattern
“peak” is…
Highest concentration of each dose
“trough” is…
Lowest concentration of each dose
as steady-state is reached the ‘peak’ value will not change day to day, nor will the ‘trough’ so if you wish to measure levels for therapeutic drug monitoring (TDM) you usually will..
choose a particular time of day and always measure it at that same time (eg. 4 hours after the morning dose)
Is the theoretical volume a drug would occupy if it was evenly distributed through the body at the same concentration as in plasma
Apparent Volume of Distribution (Vd)
Dose/Dosage
mass – e.g mg/kg
Volume of Distribution
usually L/kg
Plasma drug concentration
mg/L
A very _______ Vd suggests that the drug is not being distributed to all of the tissues
LOW
A very _____ Vd (>1L/kg) suggests that the drug is distributing preferentially to tissue and may even be sequestered somewhere
HIGH
Total Body Clearance (CLB):
The volume of distribution of drug in the body cleared of the drug per unit time (mL/min/kg) and this is the sum of clearance by the kidneys, liver and everywhere else, thus CLB takes into account both metabolism and excretion
As Vd increases t1/2 increases:
the wider a drug is distributed then it probably has more than one compartment and so that means it has to distribute back to the central compartment to be eliminated and that will take some time
If the Vd is lower than that redistribution doesn’t happen and at the same clearance rate the drug will be gone sooner (shorter t1/2). T or F?
TRUE
As Clearance increases t1/2 decreases:
if we are clearing the drug faster it will be hanging around the body for a shorter time.
