Pharmacokinetic Concepts Flashcards
What are some pharmacokinetic parameters
Half-life, clearance
What can pharmacokinetic parameters be used to predict?
Drug dose, dose intervals, dosing in renal impairment
What is the prime goal of any drug therapy?
To achieve the desired beneficial effects with minimal adverse effects.
The choice of a drug will be governed by the effect desired (pharmacodynamics)
The dose of a drug, route, formulations, frequency will be determined by the pharmacokinetic characteristics (pharmacokinetic)
Why is plasma concentrations used?
Proxy of drug concentrations. It is not feasible to routinely measure drug concentrations in other tissues/organs
How do we determine the amount of drug to give a patient to achieve the plasma concentration that will provide the optimum therapeutic effect but minimal toxocity?
By application of basic pharmacokinetic principles to our clinical reasoning
What is the therapeutic window?
The concentration of a drug where therapeutic benefits are gained from a drug within a window below which there is no therapeutic benefit and above which there are harmful effects (toxicity).
What happens to the therapeutic window of a drug between IV and oral doses?
Therapeutic window is the same but there are different absorption and elimination profiles for IV and oral delivery
What is oral bioavaliability?
Is the proportion of an administered dose of a drug which reaches the systemic circulation intact.
For IV the proportion is 100%.
What is a margin of safety?
The difference between effective dose and toxic dose
What is bioequivalent?
Different brands of drugs should be similar to the innovator brand.
What is the bioavailability calculation from IV to oral?
IV drug / Oral bioavailability
What is the bioavailability calculation from oral to IV?
IV drug x Oral bioavailability
What is cMax?
Maximum plasma concentration
What is Tmax?
Time to reach maximum plasma concentration
What is volume of distributoin?
The apparent volume that the drug would distribute to if it was found in the body in the same concentration as is found in the plasma after a single dose. Expressed as volume/L.
Gives us an idea of how readily the drug distributes from the plasma.
What is the volume of distribution (Vd) calculation?
Vd (L) = amount (dose) of drug given (mg) / Concentration of drug in plasma (mg/L)
What does a high Vd mean?
Wide distribution to the various organs and tissues
What does a low Vd mean?
The drug is restricted to the plasma and ECF - poor distributed
How does age affect Vd?
Vd is based on normal population values, these will change with age due to less body water and disease states
What is clearance?
Measures the ability of the body to eliminate the drug.
It is expressed as volume/unit of time (e.g. mL/min) and represents the volume of blood completely cleared of the drug per unit of time
What is total clearance?
Is a combination of all routes of elimination i.e. CI (total) = CI (renal) + CI (hepatic) + CI (other sites)
What is the Clearance calculation?
Vd / renal clearanceL/min = xminutes
How do you assess kidney function?
Clearance of drugs is affected by organ function especially kidneys.
Kidney function is estimated using the glomerular filtration rate (GFR) mL/min
At what GFR is kidney failure?
0-15mL/min
At what GFR is kidney disease?
15-60mL/min
At what GFR is normal kidney function?
60-120mL/min
What is the most common measure to estimate GFR?
Creatinine clearance (ClCr)
What is creatinine?
It is a waste metabolite produced by muscles from the breakdown of a compound called creatine and is produced at a relatively constant rate related to muscle mass. It is completely filtered by the kidney and not reabsorbed through the nephron.
How is eGFR calculated?
Uses serum creatinine, gender, ethnicity, & age to calculate eGFR. Is is reported in mL/min/1.73m2 i.e. body surface area of 1.73m2.
What are some limitations to the use of eGFR?
Extremes of body size, high protein diet, under 18 years, ethnicity factors not yet calculated for other ethnic groups.
What is half-life?
It is the time taken for the concentration of the drug in the plasma to increase (accumulate) or decrease (elimination) by 50% (half)
What is the half life dependent on?
volume of distribution and clearance
What is the half life calculation?
t1/2 = 0.693 Vd / Cl
What does the half life determine?
Half life determines the time to reach constant effective concentrations in the plasma and the appropriate dosing interval to maintain that concentration
What is steady state (Css)?
When the amount of drug entering the blood
What is steady state (Css)?
When the amount of drug entering the bloodstream (absorption) is equal to the mount of drug being eliminated (metabolism & excretion) from the bloodstream
How is Css determined?
By the half-life of the drug and is generally attained after approximately 4 half lives when repeated doses are given
What is the loading dose used for?
May be given to quickly attain Css, particularly if the drug has a long half-life
What is the therapeutic window?
This is the range of concentration at which the drug is therapeutically effective with the minimum unwanted side effects
What is the calculation for therapeutic index?
minimum toxic dose / minimum effective concentration
What is ED50?
Is the effective dose in 50% of the population
What is TD50?
Is the toxic dose in 50% of the population
What is target concentration?
This will be a concentration within the therapeutic window . It makes no sense to under dose, could e seen as potentially as harmful as over dosing
What is minimum effective concentration?
The minimum concentration at which a therapeutic response (pharmacodynamic effect) is obtained
What is the maximum recommended concentration (or minimum toxic concentration)
The maximum effective concentration above which toxic/unwanted side effects occur
What is the loading dose equation?
LD = volume of distribution x TC / Bioavailability
What is the maintenance dose concentration?
MD = clearance x TC / Bioavailability
What is therapeutic drug monitoring?
Sampling of drugs to ensure they are within the therapeutic index. Especially drugs with a narrow therapeutic index e.g. gentamicin, vancomycin, lithium, amiodarone, clozapine
