Clinical Pharmacokinetics

Question 0

Clearance for first order kinetics

Answer 0

=Rate of elimination of drug/plasma drug concentration
=Dose/AUC
Rate of elimination=CL x C
*defined as the volume of blood cleared per unit time

Question 1

Volume of distribution

Answer 1

Vd=Amount of drug in the body/Plasma drug concentration
=dose/C
Dose=Vd x C
* the volume required to contain all of the drug in the body at the same concentration as in the blood or plasma
High Vd=low plasma concentration
***used to calculate loading dose. thats is true purpose

Question 2

Half life

Answer 2

Time required for 50% of remaining drug to be eliminated. Constant for first order kinetics

=(.7 x Vd)/CL

It also works the same way when giving the drug. after 4 half lives you reach steady state.

CYP induction decreases half life.
Ageing, CYP inhibition, cardiac failure, liver, renal failure, obesity, pathologic fluid all increase half life

Question 3

Saturation kinetics (0 order kinetics)
*rate of elimination
Examples of some drugs

Answer 3

=(Vmax X C)/(Km + C)
Km= plasma concentration at which half of the maximal rate of elimination is reached
Vmax is equal to the maximal rate of elimination
*eventually the concentration will be significantly higher than the Km. so you can then take out the Km
**aspirin at high doses, ethanol, phenytoin

Question 4

Dosage Regiman

Maintenance dose and loading dose

Answer 4

maintanance dose must equal clearance to remain in steady state
loading dose: use Vd to determine that to reach Steady state more rapidly
dosing rate ss = elimination rate ss = CL x C/F
Maintenance dose = Dosing rate x dosing interval

Question 5

IV infusion

Answer 5

Css=Infusion rate/CL
4 infusion rates = ss
Loading dose = Vd x Css/F = maintanence dose x AF
for Constant Infusion — for intermittent dosing

Question 6

Accumulation Factor

Answer 6

predicts the ratio of the peak concentration at steady state to the peak concentration after the first dose

=1/Fraction lost in one dosing interval
PCss=PC1 x AF