PK 14: Interpatient PK & PD Variability

Question 1

Drug-Drug Interactions

Inhibition of Clearance

Answer 1

• perpetrator drug inhibits metabolism or excretory transport of victim drug, resulting in ↓ CLint
• ↓ CL of victim drug is likely to be observed (especially for low to mod E drugs)

Question 2

Drug-Drug Interactions

Induction of Clearance

Answer 2

• perpetrator drug induces (ie. increases expression) metabolism or excretory transport of the victim drug, resulting in ↑ CLint
• ↑ CL of victim drug is likely to be observed (especially for low to mod E drugs)

Question 3

Drug-Drug Interactions

Alterations in Plasma-Protein Binding

Answer 3

• perpetrator drug displaces victim drug off its plasma-protein binding site, resulting in ↑ fu,p
• this can result in two different changes towards primary PK parameters
• ↑ CL of victim drug is likely to be observed (especially for low to mod E drugs)
• ↑ V of victim drug is likely to be observed (especially drugs with V > ~30-50L)