Pharmacokinetics

Question 1

What needs to happen to a drug given extravascularly in order to be absorbed? What equation represents this?

Answer 1

Dissolution - The drug needs to dissolve in the GI tract and release the active drug before being absorbed

The Noyes-Whitney equation shows that dissolution rate can be increased by reducing particle size and increasing surface area

Question 2

What quinolone has 100% PO bioavailability? What MRSA drug has 100% PO bioavailability?

Answer 2

Levofloxacin
Linezolid

Question 3

If 100mg of a drug is administered orally and 30mg is seen systemically, what is the bioavailability?

Answer 3

30/100 = .30

30% bioavailable

Question 4

What is the equation that calculates absolute bioavailability using AUC and dose?

Answer 4

F(%) = 100 x [AUC(ex)/AUC(iv)] x [dose(iv)/dose(ex)]

Ex. Dose(ex) = 50, AUC(ex) = 8; Dose(iv) = 15, AUC(iv) = 4.2
100 x [8/4.2] x [15/50] = 57
F (absolute bioavailability) = 57%

Question 5

What is the calcium correction formula and why do we need to use it?

Answer 5

Calcium(corrected) = serum calcium + [(4-albumin) x 0.8]

(need to use since it is highly protein bound, so if albumin is low, there is increased % of unbound drug)

Question 6

What is the phenytoin correction formula?

Answer 6

Phenytoin(corrected) = total phenytoin measured / [(0.2 x albumin) + 0.1]

(need to use since it is highly protein bound, so if albumin is low, there is increased % of unbound drug)

Question 7

What does volume of distribution represents? What is the general equation to find Vd?

Answer 7

Vd relates the amount of drug in the body to the concentration measured in serum or plasma. A small Vd means the drug is confined to plasma or extracellular space. A large Vd means the drug will distribute.

Vd = amount of drug in body / concentration of drug in plasma

Question 8

What does this equation represent:

? = rate of elimination / concentration

Answer 8

This calculates clearance

Ex. patient eliminated 300mg drug over 4 hours. Concentration was found to be 12.5 after the 4 hours.

Cl = (300/4) / 12.5 -> 6L/hr

Question 9

What does this equation represent:

? = [F x Dose] / AUC

Answer 9

This calculates clearance

Ex. patient receiving 400mg gentamicin IV QD, AUC = 80

Cl = 1 x 400 / 80 -> 5L/hr

Question 10

What is the difference between first and zero order elimination?

Answer 10

First order - constant percentage of drug eliminated per unit of time (ex. 50% per hour)

Zero order - constant total amount of drug eliminated per unit of time (ex. 50mg per hour)

Question 11

When do we use the Michaelis-Menten equation? What are some principles of this type of kinetics? What are 3 drugs that display this?

Answer 11

• Use this when there is saturable or non-linear kinetics
• There is a maximal rate of metabolism (Vmax). At first, there is first order metabolism, but once the enzymes are getting saturated, metabolism slows down
• Increased dose leads to disproportional increase in concentration, since there is a max rate of metabolism -> drug toxicity
• Ex. phenytoin, theophylline, voriconazole

Question 12

What type of kinetics does phenytoin display? What dose increase should we use when the serum concentration is >7mcg/mL?

Answer 12

Since phenytoin has non-linear/saturable kinetics, we are worried about toxicity when we increase the dose. For this reason, when the serum concentration is >7mcg/mL, we should increase the dose in small increments of 30-50mg.

Question 13

How do you calculate the ke from Cl and Vd?

Answer 13

ke = Cl (L)/Vd (L)

Ex. Vd = 50, Cl = 5000
kd = 5/50 -> 0.1/h

Question 14

How do we calculate a loading dose using desired concentration, Vd, and bioavailability?

Answer 14

loading dose = [desired concentration x Vd]/F