Pharmacokinetics 5

Question 1

Pharmacokinetics

Answer 1

• The use of mathematical models to quantitate the time course of drug absoption and disposition
• Most drugs (toxins) follow first-order (logarithmic) processes for absorption and elimination
  
  • the mount of drug movement varies in direct proportion to the concentration

Question 2

First order Process

Answer 2

• First order elimination
  
  • a fixed proportion moves per unit of time
  • The mount of drug moved per time period changes, but the proportion does not
    *

Question 3

Half Life (T_1/2)

Answer 3

• Elimination (Terminal) Half-life (T_1/2)
  
  • Amount of time it takes for plasma concentration to decreas by 1/2
  • T_1/2 is constant for a first-order process
    
    • Plasma concentrations decrease in a fixed proportion per unit time
  • The T_1/2 is inversely proportional to slope
  • Elimination half-life
• INDEPENDENT f concentration (dose) and is constant —– for most drugs
• If T_1/2 changes with dose, then it is likely some absorption or elimination pathway is being saturated or inhibited
  
  • transporters
  • Metabolizing enzymes

Question 4

Important Half-lifes to Remeber

Answer 4

• 3 T_1/2 ~ 90% if the drug is eliminated
• 5 T_1/2 ~97% of the drug is eliminated
  
  • Half-life needed to reach steady state
• 7 T_1/2 ~99% of the drug is eliminated

Question 5

Changes in Dose, effects on Half-life

Answer 5

• A drug is effective until it reached 10mcg/ml.
• 1mg/kg IV dose results in a 6 hour duration of effect
• If the dose is doubled (2mg/kg), the extra drug will be elimiated in one additional half-life

However twice the inital dose concentration was acheived, increase risk of adverse effects

Therefore doubling the dose may not be the most effective way to prolong the duration of drug effect

Question 6

Volume of Distribution

Answer 6

• Apparent volume of distribution
  
  • apparent colume the drug distributes
  • Reflects the dilution of the drug after administration
• The Vd may represent a true physiologic space
• The Vd amy not represent a true physiologic space.
  
  • due to ion trapping, transporters, lipophilicity, tissue binding
• Applications:
  
  • Dose determination:
    
    • what dose do we need to achieve effective concentrations
    • What does is needed to achieve 40mg/L concentrations if the volume is 2.5L
• Vd is drug specific and often species specific.
• Vd may also me age dependent

Question 7

Clearance

Answer 7

• Clearance is the rate of drug elimination through an organ or the entire body
• Clearance of drug is total body clearance
• Glomerular Filtration Rate
  
  • GFR ml/(min*kg)
  • Dog = 4
• Changes in organ function may affect the rate of drug removal from the body
  
  • Decreased clearance results in an increased half-life
  • Increased clearance results in decreased half-life
• Changes in organ function may affect the rate of drug activation resulting in decreased efficacy