Lec51_51 PK Clinical Flashcards
What type of process is C vs t?
first order = exponential decay
How can you get linear C vs t graph?
graph log C vs t
How do you determine t 1/2 from log C vs t graph?
Choose any two concentrations that differ by multiple of 2 –> time separating each multiple of 2 is t 1/2
What can you say of two drugs if they have same slope in log C vs t graph?
they have same t 1/2
Does higher or lower slope mean bigger t 1/2?
shallower slope = bigger t 1/2
steeper slow = shorter half life
What is equation for Vd?
Vd = A/C = amount of drug / concentration in plasma
What is equation for t 1/2 in one compartment model?
t1/2 = 0.7*Vd/Cl Vd = distribution volume Cl = clearance
What is the two-compartment model?
central compartment = systemic circulation + vessel-rich tissue
peripheral compartment = slowly equilibrating tissue [adipose]
What are the two kinetic phases in two-compartment model?
early distribution phase
late elimination phase
What is happening in the early distribution phase of two compartment model?
drug being removed from central compartment by combo of distribution to peripheral compartment and elimination
What is happening in late elimination phase of two compartment model?
peripheral compartment reaches equilibrium with central, elimination is solely responsible for further decline in concentration
How do you calculate Vd after distribution is complete in two compartment model?
- slope of line of elimination phase is extrapolated to t=0 to get Co
Vd [extrap] = A/Co [extrap]
What is relationship Vd and fraction of unbound drug in plasma?
directly proportional - increased fraction unbound –> proportional increase in Vd
What happens to t 1/2 if fraction of unbound drug in plasma increases?
t 1/2 increases since Vd is increasing
How do you calculate t 1/2 in two compartment model?
choose two concentrations that differ by multiple of 2 within the elimination phase –> time between these is half life
IMPORTANT THAT BOTH CONC ARE IN ELIMINATION PHASE
What happens when drug is infused at constand rate?
C approaches steady state value Css
What is true of relationship between infusion rate and rate of elimination at Css?
infusion rate = rate of elimination
What is rate of elimination?
C*Cl
What is equation for Css?
Css = IR/Cl IR = infusion rate Cl = clearance
How does Vd affect Css?
Cd does not affect Css – but if have big Vd it will take a longer time to reach Css because bigger t1/2
How long does it take to reach Css?
After 4-5 half lives, C has reached 95% of Css
After 1 half life how what fraction of Css is reached?
50% of Css after 1 half life
if infusion rate changes from any Css to a new one, how long does it take to reach the new Css
4-5 half-lives
How long does it take to get halfway from one C to new Css?
1 half life to get 50% of the way
What is loading dose [Dl]?
Dl = Css * Vd
- administer loading dose at start of treatment to bypass accumulation time
How do you determine F [bioavailability] for oral dose?
F = AUCoral / AUCIv AUC = area under curve for time vs plasma concentration graph
How do you calculate amount of drug [A] that enters the body in oral dose from the bioavailability?
A = D*F A = area D = dose F = bioavailability
For IV administration what is F [bioavailability]? What is relationship D and A?
F = 1 D = A dose = amount since its all going straight in to blood stream
How can you calculate clearance from F?
Cl = D * F / AUC Cl = clearance D = dose F = bioavailability AUC = area under curve of time vs plasma concentration graph
If absorption is much faster than elimination how can you approximate Cmax?
Cmax = D*F/Vd D = dose F = bioavailability Vd = distribution volume
What is equation for initial C after an IV bolus?
Co = A/Vd
What does slow reabsorption do to peak drug conc in plasma [Cmax] and time it takes to reach Cmax [tmax]
slow absorption
- -> decrease Cmax
- -> increase tmax
What is difference in AUC between two drugs with same bioavailibility but different rates of absorption?
same AUC even if one has faster absorption than the other and thus lower Cmax and longer tmax
What is difference in tmax and AUC between two drugs with same absorption rate but different bioavailability?
- same tmax
- lower AUC for drug with lower bioavailability
What happens in repeated oral dosing?
- 2nd dose given before 1st dose eliminated
- drug accumulates
- as avg conc rises, rate of elimination rises
- when rate of eliminate high enough to remove all previous dose, Css[av] achieved
- time to reach Css[av] is also 4-5 t 1/2 [same as IV drug infusions]
What is equation for repeat oral dosing infusion rate?
rate in = D * F / T
D = dose
F = bioavailability
T = time interval between doses
What is equation for Css[av] for repeated oral dosing?
Css[av] = D * F / (T * Cl) D = dose F = bioavailability T = time interval between doses Cl = clearance
What is equation for Css[max] - Css[min] in oral dosing?
Css[max] - Css[min] = D*F / Vd
D = dose
F = bioavailability
Vd = distribution volume
How does slower absorption rate change fluctuations in concentration in oral dosing?
slow absorption rate causes smaller fluctuations in C
How can you use loading dose in oral therapeutic dosing?
- give loading dose as first dose to get Css[av] without having to wait
When is first order kinetics reasonable assumption?
C < < Km
What happens in drugs with C near or above Km?
rate of elimination no longer proportional to C
small increase in dose can produce large increase in C
What happens if C > > Km?
zero order relation
rate of elimination = vmax
What happens to drug if zero order kinetics?
drug accumulates because can’t reach a steady state
