Pharmacokinetics 2

Question 0

Infusion rate

Answer 0

Infusion rate=Css x Cl 
CSS-> target conc-> steady state 
Similar to repeated oral doses 
Maintenance dose= the amount removed
Pick a Css in the middle of the therapeutic window

Question 1

IV infusion

Answer 1

Administration of a drug at a constant rate-> zero order process
Elimination is first order-> opposing rising conc
Aim is to achieve a steady state plasma conc
Rate in = rate out

Question 2

Plasma profile for IV drug

Answer 2

Sharp rise of curve governed by elimination process
Time to reach plateau depends on half life
Steady state reached in 4-5 half lives
CSS changes if infusion rate changes

Question 3

Single oral dose

Answer 3

Shape of plasma profile influenced by-> rate of dissolution and rate of absorption
Rapid release:
-> rise to peak absorption and elimination
-> after peak elimination only
Normal:
Tablets-> have to dissolve first so slower conc increase/ absorption
Slow release:
-> prolonged absorption superimposed on elimination-> half life is not true elimination half life-> functional half life
-> absorption takes so long it interferes with elimination

Question 4

Bioavailability

Answer 4

F 
Fraction of does actually absorbed 
Measure differences in preparations 
Compare IV and oral plot-> compare difference of area under curve
F= AUC oral/ AUC IV 
 Dose given= amount needed/F

Question 5

Repeated oral dosing

Answer 5

To produce a steady state give close enough together that previous does hasn’t been fully eliminated
Peaks and troughs on graph-> try to make as small as possible
-> increase and then reach a steady state -> proportional to dosage interval
Blunted by slow absorption

Dose= ClxCssxtau/F
Tau->dosage interval dose/tau= infusion rate
Use to calculate how to return body conc to normal/ non toxic levels

Question 6

Steady state

Answer 6

Takes 4-5 half lives to reach
Independent of dosage
Half of previous dose/conc in body left each time
May require a loading dose-> reach steady state faster

CSS= FxD/ClxT

Question 7

Therapeutic window

Answer 7

Large-> maximal dose strategy-> give large doses at large intervals as fluctuations don’t matter
Small-> target level strategy-> must keep fluctuations to a minimal-> small doses at small intervals
Depends on half life

Question 8

Urgency of onset

Answer 8

Use a loading does for long half life drugs or if immediate effect is required
Followed by maintenance does

Question 9

Elimination half life

Answer 9

Short
large tw-> large doses at convenient intervals
small tw-> IV + loading dose
Moderate 4-12h -> initial dose then half that every half life
Long >24h -> set 24h dosage interval

Question 10

Loading dose

Answer 10

Loading does=target levelxVd/F

Question 11

Maintenance dose

Answer 11

Maintenance dose = target level x Cl/F