Test 1 Pharmacokinetics

Question 1

What is the basic principle of pharmacokinetics?

Answer 1

• The effect of a drug is related to the blood concentration of the drug.
  
  • Therefore, changes in blood concentration will modify the effect of the drug.

Question 2

Define and describe Bioavailability

Answer 2

• Fraction of unchanged drug reaching the systemic circulation after administration.
• Drugs administered by intravenous route have a bioavailability of 1, all other routes are < 1.
• Bioavailabilty is denoted in most formulas by “F”.

Question 3

How is bioavailabilty determined?

Answer 3

• Comparing plasma concentration of drug over time between IV route and other routes.
• The area under the curve (AUC) vs. time is an index of the extent of drug that enters the bloodstream and thus the body.

Question 4

What is the bioavailability equation?

Answer 4

F = AUC_oral
AUC_iv

Question 5

Define and describe Half-life?

Answer 5

• Half-life is the time needed for a 50% decrease in plasma drug concentration
• Denoted as t_1/2
• Expressed in units of time (usually hr)

Question 6

What is the Half-Life formula in a one compartment model when the elimination rate constant (k_e) is known.

Answer 6

t_1/2 = (Ln 2)/ke = (0.693)/ke

Question 7

What is the four half lives rule?

Answer 7

• A drug is considered essentially eliminated from the body after 4 half-lives.
• 94% of the drug is eliminated and only 6% remains in the body.

Question 8

Define and describe Volume of distribution

Answer 8

• The apparent volume that a drug would be distributed within the body once an equilibrium is established with palsma.
• Denoted by Vd
• Expressed in Liters or Liters/kg
• Volume of distribution is an apparent volume.

Question 9

Large volumes of distribution are an indication of a drug that is?

Answer 9

Highly lipophilic or has low protein binding.

Question 10

What is the formula for Vd?

Answer 10

Vd = Dose(iv)
C₀

Question 11

How can Vd be graphically determined?

Answer 11

Using Plasma concentration at time 0.

Question 12

Define and describe Clearance?

Answer 12

• Clearance is the volume of plasma from which a drug is totally removed per unit of time.
• Usually expressed as L/hr or mL/min
• Drug can be removed by metabolism or excretion

Question 13

Total Body clearance definition

Answer 13

Sum of all clearance values for a drug and are additive.

CL total = CL_renal + CL_hepatic + CL_other

Question 14

What is the formula for clearance?

Answer 14

CL = Ke x Vd

Question 15

Formula for clearance, when Ke = 0.693/t_1/2

Answer 15

CL = 0.693/t_1/2 x Vd

Rearranged for halflife:

t_1/2 = (0.693 x Vd) / CL

Question 16

The half life of a drug is dependent on what?

Answer 16

Clearance and Vd

Question 17

If clearance decreases and Vd stays the same what happens to half-life?

Answer 17

Half-life increases.

Question 18

Assuming a single drug administration, plasma concentration is ______ _________ to the dose administered. Provide the formula for this aswell.

Answer 18

• Directly proportional
• A = C x Vd
  
  • A = amt of drug
  • C = plasma concentration
  • Vd = volume of distribution

Question 19

Define and describe First Order Elimination Kinetics?

Answer 19

• Definition: 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.
• Elimination rate (Ke) is a constant.

Question 20

Most drugs follow what order kinetics?

Answer 20

First order Kinetics

Question 21

In First Order Kinetics the elimination rate (Ke) is a constant.

What does this mean?

Answer 21

• Fraction of drug removed at any given time is constant and independent of dose.
  
  • ​Constant fraction eliminated.

Question 22

What does a graphic examination of first order kinetics look like.

Answer 22

The semi-log plot for one compartment first order kinetics will be a straight linear line.

Question 23

Define and describe One Compartment model including what its graphical model looks like.

Answer 23

• A drug rapidly equilibrates between plasma and tissue relative to its elimination rate. The body acts as a single compartment.
• Semi-log plot of plasma concentration over time is a straight line when the drug follows first order kinetics.
• Changes in plasma concentration reflect a proportional change in tissue concentration.
  
  • ​The plasma and tissue concentrations may be different.
  • The drug does not inherently distribute to all tissues.

Question 24

Define and describe the Two compartment model:

Answer 24

• A drug takes a longer time period to establish equilibrium between plasma and tissue
  
  • Drug has two compartments for distribution:
    
    • Central and a peripheral compartment.
      
      • Drugs can move between these two freely.
    • Elimination occurs from the central compartment.

Question 25

Graphically describe the semi-log for two compartment model

Answer 25

* The semi-log plot results in two phases when the drug follows first order kinetics. * Initial distribution phase (more rapid decline in plasma drug concentration over time * Elimination phase (less severe continous decrease.

Question 26

Describe **Zero Order Kinetics**

Answer 26

* Definition: **A constant amount of a drug is eliminated _independent_ of dose; the enzymes involved in elimination are saturated.**

Question 27

Define and describe **Concentration at steady state (CSS)**

Answer 27

* **The plasma plasma concentration maintained at Steady state** * **​Attained after 4 half-lives.** * **CSS: rate of administration = rate of elimination**

Question 28

Define and describe **Maintenance Dose:**

Answer 28

* Dose taken at regular intervals to keep concentration within a trough and peak. * **The fluctuations between the peak and trough are dependent on the dosing interval.** * **The _longer_ the dosing interval the greater the variation in peak and trough values.**

Question 29

Mathematical formula for CSS?

Answer 29

* *CSS = _MD_** * *CL**

Question 30

Mathematical formula for maintanence dose

Answer 30

``` **MD = _Dose x F_ Dosing interval(t)** ``` **t = dosing interval (its actually a greek t)**

Question 31

Equation for **CSS for constant IV infusion**

Answer 31

* *CSS = _Infusion rate_** * *CL**

Question 32

# Define and describe a **loading dose**? Equation?

Answer 32

A single large dose that can be given to produce an immediate rise in plasma drug concentration. ## Footnote **Loading Dose = _CSS x Vd_ F**

Question 33

What is the Ke for a drug with a half-life of 3 hours?

Answer 33

Ke = _0.693_ = 0.231 h^-1 3h