F3 Pharmacokinetics following IV bolus administration

Question 1

what are the 2 categories of IV administration?

Answer 1

• bolus (single dose)
• infusion (constant rate)

Question 2

what is disposition?

Answer 2

everything that happens after absorption

Question 3

regarding an IV bolus, what is the most simple situation?

Answer 3

• one-compartment model for IV bolus
• the simplest model describing drug distribution and elimination

Question 4

what assumptions are made in the one-compartment model for IV bolus?

Answer 4

• the body acts like a single and uniform compartment
• the entire dose of a drug is injected at one moment (bolus dose)
• drug distributes through the entire body (compartment) instantaneously
• the volume of the compartment remains constant
• drug elimination from the body starts immediately

Question 6

after single dose IV administration, describe the plasma drug concentration

Answer 6

• the fall in plasma drug concentration is an exponential function of time (t) after dose
• concentration at any given time = initial concentration x e^ (-kt)

Question 7

what is half-life? how is its formula proven?

Answer 7

• the time taken for the plasma concentration to fall by half

Question 8

describe how half-life can be found graphically

Answer 8

Question 9

why is C0 = dose / Vd not the recommended way for calculating Vd?

Answer 9

• C0 is therefore in most cases not very accurate due to extrapolation, so we do not want to use it to find Vd

Question 10

how is clearance calculated?

Answer 10

• we take frequent blood samples after a bolus IV dose
• measure drug concentration in the plasma and plot values against time
• calculate the area under the drug concentration vs time curve (AUC)

Question 11

in order to find clearance, we need AUC. how do we do this?

Answer 11

• can be done by approximation for a finite area (only accounts up to the last place where you sample)
• can be done exactly to infinity by integration (use the trapezium rule until the last measurement then add (C last / k) to approximate what happens afterwards

Question 12

after AUC is calculated, how can Vd be calculated?

Answer 12

• after AUC is calculated, CL can be calculated (CL = dose / AUC)
• after CL is calculated, Vd can be calculated (k = CL / Vd)

Question 13

what are the 2 primary independent pharmacokinetic parameters?

Answer 13

clearance (CL)
apparent volume of distribution (Vd)

Question 14

what are the 5 steps to the IV bolus administration calculations sequence?

Answer 14

1. half-life
2. elimination rate constant
3. AUC
4. clearance
5. apparent volume of distribution