Pharmacokinetics

Question 1

Definition of Pharmacokinetics

Answer 1

Actions of the body on the drug
-absorption
-distribution
-metabolism
-elmination
Prodrug
Permeation
Diffusion
Acid-Base

Question 2

Clearance

Answer 2

• Measure of the body’s ability to eliminate the drug

- Measured in a rate

Question 3

Volume of distribution

Answer 3

• Apparent space in the body’s availability to contain the drug
• Relates the amount of drug in the body (dose) to the concentration in the blood or plasma
• Can use this concept to calculate loading doses (vanco)
• Often in liters

Question 4

Half-life

Answer 4

• also written is t 1/2- time required for 50% of the drug to be eliminated
• Will depend on volume of distribution and on clearance

Question 5

Half-life example: If the concentration of the drug in the body is 100mg/mL and the half-life is 5 hours, what will the concentration be in 10 hours?
-How long will it take the concentration to be 12.5mg/mL

Answer 5

• 10hours/(5hrs/half life)=2 half lives
• 100mg/ml/1 half life=50mg/ml
• 50mg/ml/1 half life=25mg/ml

-How long will it take the concentration to be 12.5 mg/ml?
100->50
50->25
25->12.5
3 half-lives, or 15 hours

Question 6

Bioavailability

Answer 6

• The fraction of drug absorbed
• -IV medications can be assumed to be 100%
• -IM 75-100%
• SQ 75-100%
• PO 4-<100%
• Rectal 5-<100%
• Inhalation 5-<100%
• Transdermal 80-100%

Question 7

Bioavailability may be influenced by

Answer 7

• Absorption from gut
• Hydrophilicity
• Lipophilicty
• P glycoprotein
• First-pass elmination
• Rate of absorption

Question 8

First-Pass Elimination

Answer 8

• Absorption from gut > portal blood takes drug directly to liver where portion is metabolized before even reaches systemic circulation
• Morphine almost 100% absorbed from gut. However 67% of the drug is metabolized in the first pass through the liver, thus only about 33% bioavailable to reach systemic circulation

Question 9

Dosing Considerations

Answer 9

• Target concentration: Specific dose may be recommended, weight base, steady-state
• Maintenance dose
• Loading doses

Question 10

Loading dose considerations

Answer 10

• Volume of distribution for the drug
• Patient weight
• Concentration you’re looking to achieve

Question 11

Example of loading dose calculations

• Vanco has a volume distribution of 0.7L/kg
• Pt weight 100kg
• Calculate a loading dose to achieve a concentration of 40mg/L

Answer 11

• Loading Dose=volume of distribution x desired concentration
• -Loading dose=0.7L/kg x 100 kg x 40 mg/L
• Loading dose = 70L x 40 mg/L
• Loading dose = 2800 mg

Question 12

Sites for metabolism

Answer 12

Liver is the main site of drug metabolism

• GI tract
• Kidneys
• Skin
• Lungs

Question 13

Metabolism

Answer 13

• Phase I and Phase II
• Enzymes involved: Cytochrome p-450 is primary
• Many mechanisms including hydrolysis, reduction, oxidation, and others
• Substrates
• Inducers
• Inhibitors

Question 14

Elimination

Answer 14

• Stool or Urine

- Drugs are usually excreted as % changes and % unchanged