T2 - Measurement of Drug Concentrations in Biological Specimen T2

Question 1

What is the purpose of the correlation between drug concentration measurements and pharmacodynamic outcomes?

Answer 1

To optimize pharmacodynamic responses

Question 2

How is drug concentrations collected if it is difficult to measure at the site of drug action?

Answer 2

Measured by surrogate biological samples like milk, saliva, plasma, urine, feces, tissues

Question 3

What happens if [drug] is collected in tissues?

Answer 3

May not reflect [drug] in other tissues

Question 4

What if [drug] is collected in urine?

Answer 4

It is an indirect method to ascertain the bioavailability of a drug

Question 5

How is [drug] effected when collected as feces?

Answer 5

Drugs in feces reflect unabsorbed drug after an oral dose or drug expelled by biliary secretion after systemic absorption

Question 6

What if [drug] is collected by saliva?

Answer 6

Free drug diffuse into saliva and tends to approximate free drug plasma concentration

Question 7

What are the most common and direct approaches to assessing pharmacokinetics?

Answer 7

Measurement of drug and metabolite concentrations in the serum or plasma

Question 8

How is serum obtained?

Answer 8

When whole blood is allowed to clot and after centrifugation, the supernatant is serum

Question 9

How is plasma obtained?

Answer 9

From the supernatant of centrifuged whole blood to which an anticoagulant has been added

Question 10

Is the plasma content of serum and plasma the same?

Answer 10

No

Question 11

Why do we measure [drug] in plasma?

Answer 11

1. Drug in the plasma is in dynamic equilibrium with the tissues
2. Drug in the plasma are bound to plasma proteins
3. To monitor plasma drug concentrations

Question 12

Describe the equilibrium of drug concentrations between plasma and tissues?

Answer 12

1. Plasma [drug] are good predictors of tissue [drug] but not identical
2. Changes in plasma [drug] reflect the changes of tissue [drug]

Question 13

Describe the differences of measuring bound and unbound [drug]?

Answer 13

1. Plasma protein bound can be used to measure total drug concentrration
2. Free (unbound) [drug] is measured after filtration

Question 14

What is the purpose of monitoring plasma drug concentrations?

Answer 14

1. Allows adjustment of drug dosage → to individualize and optimize therapeutic drug regimens based on PK parameters
2. Provides a guide to modify the drug dosage with disease progression as PH parameters change progressively as many disease states progress, when alterations in physiologic functions occur

Question 15

Why should we predict drug concentration at any time after drug dose?

Answer 15

1. Quite often plasma drug concentrations are good predictors of drug concentration in tissues including sites of drug actions - they can be used for dose optimization.
2. But drug concentrations in plasma and tissues are not identical.

Question 16

What does the Cmax represent?

Answer 16

The observed peak concentration of a drug in the plasma

Question 17

What does the Tmax represent?

Answer 17

Time of peak concentration of drug in plasma

Question 18

What does the Area under the curve (AUC) represent?

Answer 18

The total amount of drug absorbed into the circulation

Question 19

What are the components the time curve?

Answer 19

A: Peak concentration (Cmax)

B: AUC

C: Peak time (Tmax)

Question 20

What are the components of the time curve?

Answer 20

A: Peak level
B: Onset
C: Therapeutic window
D: Mainly metabolism and excretion
E: Mainly absorption
F: Lag
G: Duration of effect
H: Threshold for toxic effect
I: Toxic region
J: Threshold for desired effects

Question 21

What are the characteristics of the absorption rate?

Answer 21

Cmax and Tmax

Question 22

What affects the Cmax and Tmax?

Answer 22

Drug dissolution and release of dosage form

Question 23

Why are Cmax and Tmax not used as pure measures of the absorption rate?

Answer 23

They are single-point estimates and doesn’t account for all data sampled during the absorption process

Question 24

What make Cmax clinically relevant?

Answer 24

Peak plasma concentration is related to maximal pharmacological effects or adverse effects

Question 25

What is AUC used for?

Answer 25

1. To evaluate the extent of absorption
2. Used to compare bioavailability differences between
   a. Brand and generics of drugs of the same dosage form
   b. Different dosage forms of a drug

Question 26

What factors affects AUC?

Answer 26

Formulation for the dosage form

Question 27

What factors play into AUC?

Answer 27

1. Bioavailability
2. Systemic drug clearance
3. Dose
4. AUC = Dose/CL

Question 28

What does this curve indicate?

Answer 28

1. No drug absorption involved in IV bolus
2. Assumes drug distribution is instantaneous (the moment it’s injected
3. Distribution is non-existent
4. Represents metabolism + excretion

Question 29

What do these curves indicate?

Answer 29

1. Occurrence of drug absorption until Cmax is achieved
2. Drug then undergoes disposition (distribution+elimination+excretion) slower paces that absorption

Question 30

Which of the graphs has the slowest absorption?

Answer 30

Rectal. The longer (wider) the Tmax the slower the absorption

Question 31

Which of the graphs has the faster absorption?

Answer 31

Inhalation, the curve is closer to y-axis.

Question 32

What do these curves indicate?

Answer 32

1., IV infusion, drug absorption is slower and tmax is delayed and disposition (distribution+elimination) declines slowly
2. IV infusion is continuing to rise