Pharmacokinetics 8

Question 1

Individual Variability in Pharmacokinetics

Answer 1

• In addition to species differences in pharmacokinetics, intraspecies vairability in pharmacokinetics also occurs
  
  • Random Variability
    
    • Hepatic blood flow, amount of metabolizing enzymes, glomerular filtration rates, cardiac output, blood pressure, plasma protein content
  • Polymorphisms and Genetic Differences
    
    • Polymorphism
      
      • Extensive Metabolizer (EM):
        
        • Normal
        • 2 copies of the gene
      • Poor Metabolizer (PM):
        
        • Decreased expression of metabolizing enzymes
        • < 2 copies of the gene
      • Ultrametabolizer (UM):
        
        • Greater than normal expression of metabolizing enzymes
        • > 2 copies of the gene
  • Drug metabolizing enzymes, Drug transporters, polycystic Kidney Disease

Question 2

Variability of Pharmacokinetic data

Answer 2

PK data are vairable within a species / breed

T_1/2 range form 1.-1.6

Cmax 112-218 ng/ml