Exam 1 IV Bolus Flashcards
What is pharmacokinetics?
the study of the process by which a drug is absorbed, distributed, metabolized, and excreted by the body (what the body does to the drug!)
Where is the major site of drug absorption?
the small intestine where the drug is in formulation
Where is the major site of drug metabolism?
liver
Where is the major site of drug distribution?
the systemic circulation where drug is bound to proteins or is free and could be distributed in other tissues as well
Where is the major site of drug excretion?
kidney
If a drug is lipophilic, what will it tend to bind to?
proteins such as albumin
What do we measure when we study PK?
drug concentration in the blood
What is the optimal drug therapy?
the determination of optimal dosage regimen because if concentration is too high, may cause toxicity and if the concentration is too low, there may not be any pharmacologic effect
What does the stereotypical graph of plasma drug concentration v time look like?
is downwards linear line
What is an IV bolus?
a rapid injection that ensures the entire dose enters the systemic circulation immediately → if drug goes directly into the vein, it can go to the heart and then travel throughout systemic circulation
What are the two major drug elimination pathways?
liver and kidney
What is kel?
the slope of the line of a plasma drug concentration v time graph
A larger kel value means what in terms of elimination?
larger kel = faster elimination
What should we assume about the one compartment model?
the body acts like a single homogenous compartment and that the drug rapidly distributed uniformly in it → drug distribution occurs as soon as drug is given to the patient
What else do we assume about the one compartment model?
- the drug is in rapid equilibrium between the blood and the tissues
- changes in the plasma concentration of drug will result in proportional changes in tissue drug levels
- drug concentration in the compartment is the same as plasma drug concentration
Elimination of the drug in a one compartment model follows what process?
first order process → the elimination rate is proportional to the concentration (or amount) of the drug
What is the difference between zero order elimination and first order elimination?
zero order kinetics follow a constant elimination rate that is independent of the drug concentration while first order kinetics follow an elimination rate that is dependent on drug concentration
What are the equations associated with first order kinetics?
dA/dt = -kel*A (where A is drug amount in the body and dA/dt is elimination rate) A = A0*e^-kel*t (where A0 is the drug amount at time 0, t is time, and kel is the elimination rate constant)
What is the elimination rate constant (kel)?
it is a proportionality constant relating rate of elimination and the amount of drug in the body → is a drug specific property and has units of /time such as /min or /h
What is volume of distribution (Vd)?
it is the size of the compartment which is estimated based on plasma drug concentration → a drug specific property and has units of volume like mL or L
Drug concentration in the compartment is equal to what?
plasma drug concentration
The amount of drug in the body (A) is equal to what?
volume of distribution (Vd) multiplied by plasma drug concentration (Cp)
Why is volume of distribution important?
a parameter that helps us understand the relationship between drug amount in the body (A) and drug concentration (C) → Cp = Cp0e^-kelt
When graphing the drug concentration v time plot, what does the graph look like?
curved downwards line (Cartesian plot) → but if use a semi log plot then it becomes a downward linear line
What is the y intercept of the concentration v time plot?
Cp0
Immediately after an IV bolus dose, what is the dose equal to?
dose = Vd*Cp0
Different drugs have what different values?
different Cp0 after a given dose and thus a different Vd (since those are drug specific parameters) → Vd depends on the physicochemical properties of the drug
What are some things to know about hydrophilic compounds?
- does not cross lipid bilayers readily
2. higher Cp0 given a dose → has a lower Vd since it has worse tissue distribution
What are some things to know about lipophilic compounds?
- has better tissue distribution
2. lower Cp0 given a dose → larger Vd because of better tissue distribution
What are some important things to know about Vd?
- Vd dose does not correspond to to a physiologic volume
- when there is extensive tissue distribution, Vd > 100 L is common and Vd > 10000 L is possible
- special occasion → if drug is confined to the bloodstream (volume is about 5 L) or total body water (volume is about 42 L) then the Vd value may reflect the physiologic volume → example is with antibodies which are large molecules
How can you find kel using data points from the graph/table?
kel = -ln(Cp2)-ln(Cp1)/t2-t1
What is half life?
the time it takes for half of the drug in the body to be eliminated or the time it takes for the plasma concentration to decrease by half → has units of time like h or min
What is the equation for half life (t1/2)?
t1/2 = ln(2)/kel = 0.693/kel
What is the fraction remaining in the body?
the fraction of the dose remaining in the body (has not been eliminated from the body) → has no unit and can be expressed as a percentage
What is the fraction remaining in the body equation?
e^-kel*t OR (1/2)^n where n is the number of half lives
What is the equation given for the fraction of dose eliminated from the body?
1-e^-kel*t OR 1-(1/2)^n
What is the percent remaining and percent eliminated for the following half lives?
1 half life → 1/2 remaining, 1/2 eliminated
2 half lives → 1/4 remaining, 3/4 eliminated
3 half lives → 1/8 remaining, 7/8 eliminated
What does a large kel value signify?
drug elimination is faster so there is a shorter half life → higher kel value means steeper slope!!
What is clearance (CL)?
the proportionality constant relating the rate of drug elimination and the plasma concentration → has units of volume per unit of time (mL/min or L/h)
What is the equation for clearance (CL)?
CL = kel*Vd = dose/AUC
A larger clearance value means what?
that the drug gets eliminated faster
Drug A Drug B
kel > kel
CL > CL
Drug A gets eliminated faster than Drug B since Drug A has a larger kel value and a larger CL value
What is the most important thing to note about kel?
it represents the fractional rate of loss of drug from the body → aka the % of drug eliminated per unit of time → example is if kel = 0.1 then 10% of the drug is lost or eliminated per hour OR kel = 0.5 then 39% of the drug is lost or eliminated per hour
Both kel and CL are terms to describe elimination, but what is the difference between the two parameters?
- kel is the fractional rate of drug loss from the body
2. clearance is the volume of drug containing plasma from which drug is completely cleared
Both kel and CL are terms to describe elimination, but what is the difference between the two parameters?
- kel is the fractional rate of drug loss from the body → IS A RATE
- clearance is the volume of drug containing plasma from which drug is completely cleared → IS VOLUME/TIME
Why can’t clearance (CL) exceed cardiac output (about 5 L/min)?
drugs reach the drug eliminating organs via the blood pumped by the heart
When calculating slope (kel), what points should you use?
use the points on the best fit line (from the log scale graph), not the actual data points
What is AUC and how is it calculated?
it is the area under the concentration curve of the concentration v time graph → for a specific time value (ex. 10 hour and 5 hours), AUC can be calculated using the following equation: AUC = ((Cpn+Cpn+1)/2)*(t3-t2) and then to get the AUC, have to add up all of the area
For a drug that follows linear kinetics, what happens to the concentration as the dose is doubled?
if dose is doubled, the plasma concentration will double at each time point
For linear kinetics, which pharmacokinetic parameters are constant and independent of dose?
kel, CL, and Vd
What happens with nonlinear kinetics?
- it is dose dependent
- happens when one or more of the ADME processes shows saturation → example is hepatic metabolism of a drug is saturated in a typical dose range
Which pharmacokinetic parameters are dose dependent for nonlinear kinetics?
clearance and volume of distribution
With the one compartment linear model, what happens to Vd if the dose is higher?
not change!
True/false: In linear kinetics, AUC is proportional to dose.
true (CL = dose/AUC)
As time passes after drug administration, CL, kel, or Vd will…
not change! (these are parameters that are independent of dose and stay constant)
