Lec51_51 PK Clinical

Question 1

What type of process is C vs t?

Answer 1

first order = exponential decay

Question 2

How can you get linear C vs t graph?

Answer 2

graph log C vs t

Question 3

How do you determine t 1/2 from log C vs t graph?

Answer 3

Choose any two concentrations that differ by multiple of 2 –> time separating each multiple of 2 is t 1/2

Question 4

What can you say of two drugs if they have same slope in log C vs t graph?

Answer 4

they have same t 1/2

Question 5

Does higher or lower slope mean bigger t 1/2?

Answer 5

shallower slope = bigger t 1/2

steeper slow = shorter half life

Question 6

What is equation for Vd?

Answer 6

Vd = A/C = amount of drug / concentration in plasma

Question 7

What is equation for t 1/2 in one compartment model?

Answer 7

t1/2 = 0.7*Vd/Cl 
Vd = distribution volume
Cl = clearance

Question 8

What is the two-compartment model?

Answer 8

central compartment = systemic circulation + vessel-rich tissue
peripheral compartment = slowly equilibrating tissue [adipose]

Question 9

What are the two kinetic phases in two-compartment model?

Answer 9

early distribution phase

late elimination phase

Question 10

What is happening in the early distribution phase of two compartment model?

Answer 10

drug being removed from central compartment by combo of distribution to peripheral compartment and elimination

Question 11

What is happening in late elimination phase of two compartment model?

Answer 11

peripheral compartment reaches equilibrium with central, elimination is solely responsible for further decline in concentration

Question 12

How do you calculate Vd after distribution is complete in two compartment model?

Answer 12

• slope of line of elimination phase is extrapolated to t=0 to get Co
  Vd [extrap] = A/Co [extrap]

Question 13

What is relationship Vd and fraction of unbound drug in plasma?

Answer 13

directly proportional - increased fraction unbound –> proportional increase in Vd

Question 14

What happens to t 1/2 if fraction of unbound drug in plasma increases?

Answer 14

t 1/2 increases since Vd is increasing

Question 15

How do you calculate t 1/2 in two compartment model?

Answer 15

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

Question 16

What happens when drug is infused at constand rate?

Answer 16

C approaches steady state value Css

Question 17

What is true of relationship between infusion rate and rate of elimination at Css?

Answer 17

infusion rate = rate of elimination

Question 18

What is rate of elimination?

Answer 18

C*Cl

Question 19

What is equation for Css?

Answer 19

Css = IR/Cl
IR = infusion rate
Cl = clearance

Question 20

How does Vd affect Css?

Answer 20

Cd does not affect Css – but if have big Vd it will take a longer time to reach Css because bigger t1/2

Question 21

How long does it take to reach Css?

Answer 21

After 4-5 half lives, C has reached 95% of Css

Question 22

After 1 half life how what fraction of Css is reached?

Answer 22

50% of Css after 1 half life

Question 23

if infusion rate changes from any Css to a new one, how long does it take to reach the new Css

Answer 23

4-5 half-lives

Question 24

How long does it take to get halfway from one C to new Css?

Answer 24

1 half life to get 50% of the way

Question 25

What is loading dose [Dl]?

Answer 25

Dl = Css * Vd | - administer loading dose at start of treatment to bypass accumulation time

Question 26

How do you determine F [bioavailability] for oral dose?

Answer 26

``` F = AUCoral / AUCIv AUC = area under curve for time vs plasma concentration graph ```

Question 27

How do you calculate amount of drug [A] that enters the body in oral dose from the bioavailability?

Answer 27

``` A = D*F A = area D = dose F = bioavailability ```

Question 28

For IV administration what is F [bioavailability]? What is relationship D and A?

Answer 28

``` F = 1 D = A dose = amount since its all going straight in to blood stream ```

Question 29

How can you calculate clearance from F?

Answer 29

``` Cl = D * F / AUC Cl = clearance D = dose F = bioavailability AUC = area under curve of time vs plasma concentration graph ```

Question 30

If absorption is much faster than elimination how can you approximate Cmax?

Answer 30

``` Cmax = D*F/Vd D = dose F = bioavailability Vd = distribution volume ```

Question 31

What is equation for initial C after an IV bolus?

Answer 31

Co = A/Vd

Question 32

What does slow reabsorption do to peak drug conc in plasma [Cmax] and time it takes to reach Cmax [tmax]

Answer 32

slow absorption - -> decrease Cmax - -> increase tmax

Question 33

What is difference in AUC between two drugs with same bioavailibility but different rates of absorption?

Answer 33

same AUC even if one has faster absorption than the other and thus lower Cmax and longer tmax

Question 34

What is difference in tmax and AUC between two drugs with same absorption rate but different bioavailability?

Answer 34

- same tmax | - lower AUC for drug with lower bioavailability

Question 35

What happens in repeated oral dosing?

Answer 35

- 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]

Question 36

What is equation for repeat oral dosing infusion rate?

Answer 36

rate in = D * F / T D = dose F = bioavailability T = time interval between doses

Question 37

What is equation for Css[av] for repeated oral dosing?

Answer 37

``` Css[av] = D * F / (T * Cl) D = dose F = bioavailability T = time interval between doses Cl = clearance ```

Question 38

What is equation for Css[max] - Css[min] in oral dosing?

Answer 38

Css[max] - Css[min] = D*F / Vd D = dose F = bioavailability Vd = distribution volume

Question 39

How does slower absorption rate change fluctuations in concentration in oral dosing?

Answer 39

slow absorption rate causes smaller fluctuations in C

Question 40

How can you use loading dose in oral therapeutic dosing?

Answer 40

- give loading dose as first dose to get Css[av] without having to wait

Question 41

When is first order kinetics reasonable assumption?

Answer 41

C < < Km

Question 42

What happens in drugs with C near or above Km?

Answer 42

rate of elimination no longer proportional to C | small increase in dose can produce large increase in C

Question 43

What happens if C > > Km?

Answer 43

zero order relation | rate of elimination = vmax

Question 44

What happens to drug if zero order kinetics?

Answer 44

drug accumulates because can't reach a steady state