L44 - IV Infusion 2

• Give an eqn to work out Css.

  
  

  When can we use this?

  Css = R / Cl.

  
  

  OR Css = R / k x V.

  
  

  Use at plateau (steady state).

  
• Give an eqn to work out C post infusion.

  Cpost = C0 x e^-ktpost inf.

  
  

  Where C0 = Css.

  
• How can we predict when steady state will be achieved?

  
  

  What does time taken to reach a fraction of steady-state depend on?

  C = Css (1-e^-kt).

  
  

  Time taken to reach a fraction of steady state depends only on t1/2 (Cl and V) of a drug.

  
• How can we find F, the fraction of equilibrium attained at a given time of the infusion?

  F = C / Css

  
• How can we find the time taken to reach the value of F?


  ln (1-F) = -k x t.

  
  

  Can also use A = A0 x e^-kt

  
• Which factors control the time to reach the plateau/ steady state?

  Clearance and volume of distribution of a drug.

  
  

  t1/2 = 0.693/k = 0.693 x V/Cl

  
• In exam, if asked to find the time to reach steady state where there is no F given, how many half lives should be used?

  Any value from 4x t1/2 will be correct unless a specific F is specified.
• How many half lives do we need to reach Css?

  Usually 4-5 half lives. (95% of plateau)
• In


  IV Bolus, what are the advantages and disadvantages of achieving and maintaining a high conc?- Highest [drug] on injection at t=0.

  
  

  - Achieves required [conc] immediately.

  
  

  - BUT [drug] declines continually al eliminated drug is not replaced.

  
• In


  IV Infusion, what are the advantages and disadvantages of achieving and maintaining a high conc?- [drug] starts at 0 and builds up towards Css.

  
  

  - If Crequired is Css, then 4-5 t1/2s are required.

  
  

  - Once Css is attained, it's maintained as the infusion replaces the drug eliminated.

  
• If using IV Bolus and infusion together, what can we assume?

  
  

  What's the eqn for total [drug]?

  - Due to linear kinetics, assume that [drug] from IV bolus and [drug] from IV infusion behave independently.

  
  

  C = (C0 x e^-kt) + (Css(1-e^-kt)).

  
  

  A (total) = A (bolus) + A (infusion).

  
• What are the benefits to using bolus + infusion?

  Gain effective conc earlier, and keep it constant!
• Give an eqn to find C0 in IV bolus.

  C0 = dose / Vd.

  
• Why might it be necessary to modify infusion rate?

  Bc inadequate therapeutic response, or toxicity.

  
• After a new infusion rate, R, what does time to reach Css depend on?

  
  

  How can we predict new [drug]?

  - Time to reach Css depends only on t1/2 of drug.

  
  

  - Infusion 1 with initial R is stopped, and infusion 2 with new R starts at the time infusion 1 was stopped.

  
  

  - At any time, [drug] will be the sum of the conc remaining from 1st infusion PLUS that due to 2nd infusion.