Area under the curve

Question 1

What is the AUC?

Answer 1

Total systemic exposure -> resulting in a pharmacological effect

Question 2

What factors does the AUC depend on?

Answer 2

-Dose administered (larger dose, more exposure (AUC)

-Rate of Elimination

Question 3

What is AUC used for?

Answer 3

Useful when evaluating if two formulations (capsule, tablet) of the same dose result in equal tissue exposure

-manufacturing of generic drugs

Question 4

What does the AUC curve look like with reference to drug formulations?

Answer 4

IV: Instant peak, dropping fast bc the drug reaches systemic circulation quickly therefore is eliminated quickly
oral, transdermal,..: slow rising to peak, slower drop

Question 5

What are the parameters that can be calculated with the AUC?

Answer 5

• Clearance = Dose / AUC !!
• Systemic Bioavailability
• Steady-state Volume of Distribution
• Average concentration over a steady-state interval

Question 6

How does Clearance relate to AUC?

Answer 6

The faster the drog gets cleared the less it is exposed to the body (lower AUC)

Question 7

How is the AUC calculated?

Answer 7

• The sum of the area of the trapezoids (rectangle) + the final trapezoid which has no last concentration point to draw a trapezoid (C0 / k)
• Trapazoid -> Rectangle (midpoints of concentration)

Area of rectangle = b * h (a * b)

Question 8

Why can’t AUC be calculated using single concentrations?

Answer 8

It will result in an overestimation of AUC

->Use average of two concentrations -> between 10 and 20 mg/L -> 10 + 20 = 30 / 2 = 15

Question 9

Why is the trapezoidal approach just an estimate?

Answer 9

There are areas of overestimation and underestimation, which roughly cancel each other out

Question 10

How can the error of estimation be minimized?

Answer 10

By using more concentration points and creating more rectangles

Question 11

What is another way to calculate the AUC?

Answer 11

AUC = C0 / k

only possible for IV administration -> for oral administration there is no C0

Question 12

How is the final trapezoid calculated?

Answer 12

C0 * k
-> The last peace is a triangle

Question 13

What is the formula to calculate the AUC using the trapezoidal approach?

Answer 13

AUC = SUM 1/2 (C1 + C2) (t2 - t1) + C0 * k

Question 14

How is the average concentration Css calculated?

Answer 14

Total AUC / dose interval (f.e dose given q 6hr)