PD Principles: Drug-Receptor Interactions and Dose Response Curves; Dosing: Target Concentration

Question 1

Achieving the Target Concentration:

Answer 1

Loading dose
• A single or series of doses to rapidly achieve the target Cp
• Requires knowing: [Target], Volume of distribution (Vd), and bioavailability (F) of the drug
– Parameters are a starting point for initial predictions

Question 2

Maintaining the Target Concentration:

Answer 2

Dosing rate
• Achieving a rate of input = rate of loss
– Maintains a steady state CP
 • Requires knowing: [Target], clearance and bioavailability (F) of the drug
– Patient specific parameters may affect clearance

Question 3

Maintaining the Target Concentration:

Answer 3

Maintenance dose
• Achieving a rate of input = rate of loss
– Maintains a steady state CP
• Considers time between dosing (QD, BID, QID, …)

Question 4

Minimizing Concentration Fluctuations:

Answer 4

Dosing interval
• Minimize fluctuations in Cp
• Need to consider safe therapeutic and toxic limits for a drug
– Patient specific parameters may affect clearance

Question 5

PK Summary:

Answer 5

• Rational dosing will consider PK and PD
• Drug accumulation relates to half-life and dosing frequency
• Drug effects may not directly reflect changes in Cp
• Parameters in dosing calculations to achieve and maintain target Cp