Pharmacokinectics: Quantitative Flashcards
What is pharmacokinetics?
- study of time-dependent changes of drug and metabolite concentrations in blood and body fluids
What is the therapeutic index?
Therapeutic Index =
What is the difference between pharmacokinetics and pharmacodynamics?
pharmacokinetics: body’s effect on drug
pharmacodynamics: drug’s effect on body
What are zero-order kinetics?
the rate of absorption or elimination of drug is constant, not dependent on drug concentration between where the drug is vs. where it’s going
M =kt
[M= amount of drug absorbed/ eliminated, t = time]

What are first-order kinetics?
rate of absorption or elimination is proportional to the drug concentration gradient (drug still unabsorved/ uneliminated)
M=M0e-kt
[M is the amount of absorbed/ eliminated drug, M0 is initial amount at the absorption/ elimination site, k is the elimination rate constant]

Define Volume of Distribution Vd.
- theoretical volume in which drug is distributed
-
Vd = amount of drug in body (mg) / concentration of drug in plasma (mg/L)
[unit: L, unless written as Vd L/body weight] - Vd can be larger than actual body volume, meaning drug disperses to other body compartments
- Blood plasma = 3.5 L, Blood volume = 5.5 L,
ECM water = 13 L
- Blood plasma = 3.5 L, Blood volume = 5.5 L,

How can Vd be extrapolated from a concentration vs. time chart?
Vd = dose given at t=0/
extrapolated y-axis concentration of drug at time=0
Define Clearance.
volume of plasma cleared of drug, by all routes, per unit time
CL = rate of elimination (mg/hr) / plasma concentration of drug (mg/L)
[units: L/hr]
What is the relationship between clearance and volume of distribution?
CL = Vd x ke (elimination constant)
Define half life t1/2.
time required to change amount of drug in the body by 1/2
t1/2 = 0.693 x Vd / CL
low clearance, longer half-life
Define bioavailability (F).
fraction of unchanged drug reaching the systemic circulation after oral administration; dependent upon how well drug is abosbed from gut and how much is extracted by liver
F = f (1-ER)
[f= fraction/ extent absorbed from gut, ER = extraction ratio in liver]

Define steady state.
point at which adding an additional dose of a drug will result in the same peak and trough concentrations of drug as the last dose administration

Steady State Concentration RULE OF THUMB
time it takes a drug to reach steady state concentration in intermittent doses (or intravenous dosing) after the first dose
= 4-5 half lives
This is true no matter what you do to concentration (even doubling or tripling it)
Define drug accumulation & accumulation factor. What does it predict?
- drugs are repeatedly administered: if dosing interval is shorter than four half-lives, accumulation of drug is detectable
- accumulation factor = 1/ fraction of drug lost in one dosing interval
- ex. for a drug given once every half life, AF = 2
- can predict steady state concentration: peak concentration at steady state = peak concentration after first dose x AF
Define dosing rate.
Dosing Rate = CL x CSS
[units: mg/ hr]
volume of plasma cleared of drug x concentration of drug in that volume
CSS: concentration of drug at steady state
CL: important b/c = proportionality constant between dose rate and steady-state drug concentration in plasma
Define maintenance dose. How is dosing interval determined? When is intermittent dosing not practical?
If drug is given in intermittent doses,
**Maintenance Dose = dosing rate x dosing interval
= CL x CSS x dosing interval **
dosing interval: determined by how much fluctuation in CP can be tolerated w/o inducing toxicity (smaller and more frequent vs. larger and less frequent doses)
half-life: if t1/2 for drug is <4 hrs, periodic dosing is not practical and constant infusion must be adopted
Define Loading Dose.
Loading Dose = Vd x TC
What are the steps to design and optimize a dosage regimen?
- Identify target concentration that will produce therapeutic effect
- Determine Vd and CL values for patient
- Calculate maintenance dose to keep steady state level of drug in body (amount given = amount eliminated)
- If target concentration needs to be reached quickly, loading dose might be applied
- Check whether the calculated maintenance and loading doses actually elicit the desired effect. If not, adjust the doses accordingly – the clearance might be different from the expected value