Topic 3

Question 1

Sampling Times

Answer 1

• Important to obtaining good information on the early exposure, peak exposure, peak time, and decline of the concentration-time curve after an extravascular dose
• 3 to 4 samples on the rising part of the curve and 2 to 3 points near the true peak time are needed

Question 2

Blood To Plasma Concentration Ratio

Answer 2

• The drug concentration in whole blood (Cb) is usually within a factor of two of that in plasma (C, bound and unbound)
• Occasionally, the ratio of whole blood to plasma concentration is much greater than 1.0 due to binding to blood cell components

Question 3

What is k?

Answer 3

• Rate constant of elimination of a process
• Units are expressed in per unit time (i.e. hr -1)
• Related directly to half-life (t1/2): amount of time it takes for concentration or amount of drug in the body to drop by half
• By default, k (without a subscript) is the elimination rate constant

Question 4

Window of Therapeutic Concentrations

Answer 4

• Assume that a certain window of plasma concentrations will give the optimal therapeutic response
• When the concentration is too high there is a high probability of adverse events
• When the concentration is too low there is an unacceptably high probability of a subtherapeutic response
• The concentrations between the two are referred to as the therapeutic concentration window

Question 5

What is Hematocrit?

Answer 5

• Packed-cell volume as a fraction of total volume after anticoagulation of whole blood
• (Volume of RBC)/(Total blood volume)
• Typical value is around 0.45
• Males tend to be higher

Question 6

What is fraction unbound (fu)?

Answer 6

• Cu/C or [drug]unbound / [drug]plasma
• Fraction unbound values range from 0 to 1
• Low fu → drug mostly bound to plasma protein
• Normally protein is albumin

Question 7

What is partition coefficient (ρ)?

Answer 7

• Ratio of drug concentration
• Cbc/Cu or [drug]blood cell / [drug]unbound
• ρ can range from 0→∞
• Low ρ → drug may have problem getting into RBC
• High ρ → drug freely gets into RBC

Question 8

What is fu∙ ρ?

Answer 8

• [drug]blood cell/[drug]plasma
• Low fu∙ρ → more drug in plasma
• High fu∙ρ → more drug in blood cell

Question 9

Plasma

Answer 9

Whole blood is centrifuged after adding an anticoagulant. Cells are precipitated by the centrifugation. The supernate, plasma, contains plasma proteins that often bind drugs. The plasma drug concentration includes drug bound and unbound to plasma proteins.

Question 10

PK Analysis Performed on Blood

Answer 10

• Blood is a more direct measurement than urine Drug distributes more readily in blood
• Drug is eliminated from body mainly by blood
• Blood reaches more parts of the body
• PK parameters are based on drug characteristics in blood