Pharmacokinetics

Question 1

Pharmacokinetics:

Answer 1

The quantitative expression of the relationship between absorption, distribution and elimination of drugs as a function of time.

Question 2

One compartment model:

Answer 2

A drug rapidly equilibrates between plasma and tissue relative to its elimination rate.
- Semi-log plot of plasma concentration over time is a straight line when the drug follows first order kinetics.

Question 3

Two compartment model:

Answer 3

A drug takes a longer time period to establish equilibrium between plasma and tissue.
- Drug has 2 compartments for distribution: central and peripheral.
- The semi-log plot results in two phases when the drug follows first order kinetics.
+ Initial distribution phase –> elimination phase.

Question 4

First order kinetics:

Answer 4

The rate of decrease in drug concentration is directly proportional to the amount of drug in the body.

• A constant fraction of the drug is eliminated.
• Enzymes are not saturated yet.
• Semi-log plot for one compartment 1st order kinetics = straight line.

Question 5

Zero order kinetics:

Answer 5

A constant amount of drug is eliminated independent of dose.

• Enzymes are saturated.
• ETOH and ASA.
• Concentration is a straight line on a linear scale.

Question 6

Bioavailability:

Answer 6

Fraction of unchanged drug reaching the systemic circulation after drug administration.

• IV: F = 1
• F = AUC-oral/ AUC-iv

Question 7

Importance of bioavailability:

Answer 7

• Comparison of different products with the same active ingredients.
• Method to assess influence of food on drugs bioavailability.

Question 8

Half-life:

Answer 8

t1/2 = 0.693/Ke = (0.693 x Vd) / CL

Question 9

Fraction eliminated:

Answer 9

1 - 1/(2^n)

- n = number of half-lives.

Question 10

Volume of distribution:

Answer 10

Vd: the apparent volume that a drug would be distributed within once an equilibrium is established with plasma.

• Vd = Dose (iv) / C0
• C0 = Dose (iv) / Vd

Question 11

Clearance:

Answer 11

CL: the volume of plasma from which a drug is totally removed per unit time.

• L/hr or mL/min
• CL = Ke x Vd

Question 12

Concentration at steady state:

Answer 12

Css

• First order kinetics.
• The avg plasma concentration maintained at Steady State.
• After 4 half-lives.
• Css = MD/CL
  
  • MD = maintenance dose
  • CL = clearance
• Css(iv) = (Infusion rate) / CL

Question 13

Maintenance dose:

Answer 13

MD

- MD = (Dose x F) / (Dosing interval)

Question 14

Loading dose:

Answer 14

A single large dose give to produce an immediate rise in plasma drug concentration.
- Loading dose = (Css x Vd) / F