L42 - IV Bolus 2

• Define the apparent Volume of Distribution Vd.

  - The apparent volume into which a drug distributes into the body at equilibrium.

  
• What's the eqn relating Cplasma and amount of drug to Vd?


  V = Amount of drug (A) / Cplasma.

  
• How can we find bolus dose needed? Give eqn.

  Bolus dose = Vd x Crequired.

  
• What does calculating V require?

  - An achieved equilibrium of distribution.

  
  

  (Equilibrium achieved at t=0 bc one compartment distribution is instantaneous (bolus)

  
  

  - Knowing A and Cplasma at the same time - time 0!

  
• What is C0? What does it result from?

  C0 = initial plasma conc resulting from instantaneous distribution of the dose into the Vd.

  
• Give the eqn relating rate of drug elimination (dA/dt) to [plasma] conc (Cp).

  dA/dt = Cl x Cp

  
• Give the eqn describing how [drug] conc (Cp) evolves following an IV Bolus injection.

  Cp = C0 a e^-kt

  
• Give an equation linking elimination rate (dA/dt) and Amount of drug (A)


  dA/dt = K x A

  
• Give and eqn for Amount of drug in the body following an IV Bolus administration.

  A = A0 x e^-kt

  
• Give the eqn linking Clearance (Cl), elimination rate constant (k) and Volume of Distribution (V).

  Cl = k x V

  
• Define elimination half life.


  Time required for [drug] conc and amount of drug in body to fall by 1/2.

  
• What can elimination t1/2 be used to predict?

  - How quickly Cp will decline.

  
  

  - How quickly A will decline.

  
  

  - Time to reach Css in IV infusion.

  
  

  - Time to reach Css in a multiple dose regimen.

  
• What can AUC be used for?

  - Determine clearance.

  
  

  - Estimate bioavailability of extravascular formulation.

  
  

  - Compare bioavailability of 2 formulations.

  
• Give the eqn linking AUC and initial conc C0.


  AUC = C0/k

  
• Give the Eqn linking AUC and Clearance.


  AUC = Dose/Cl.

  
  

  
  

  AUC = D / k x V

  
• Which is the preferred method to estimate clearance and why?

  - AUC bc it's model independent.

  
  

  - Regardless of whether graph is linear or not.

  
  

  - Cl = k x V is only appropriate when graph is linear and well described by one compartment model.
• How do we estimate AUC?

  The sum of the area of each trapezoid.

  
• How do we find the area of a trapezoid?

  (B + b)h/2

  
• How can we find the area of the last graph segment which isn't trapezoidal?

  AUC = Cn / k.

  
  

  where Cn = last measures conc.

  
• What are the alternative eqns to find AUC?

  
  

  When can this be used?

  AUC = C0/k.

  AUC = D/Cl.

  Used when:- only process occurring iselimination(eg in IV Bolus, post infusion phase, or terminal phase of extravascular administration).

  - Drug PKs arelinearand well-described by theOne compartment model.
• Describe applications of AUC in a) IV and b) Extravascular administration.

  a)IV: AUC reflects max body exosure to dose. Complete dose enters circulation. Cl is constant.

  b) Extravascular: AUC describes bioavailability and reflects extent of absorption.
• What is absolute bioavailability?

  Ratio of AUC obstained with an extravascular formulation and AUC IV.
• Give the Equation for absolute bioavailability comparisons (F).

  F = (AUC oral / Dose oral) / (AUC IV / Dose IV)

  
• Give the eqn for extravascular AUC.

  AUC = F x Dose / Cl

  
• How do you know whether to use one compartment or two compartment models?

  - Plot semi-log data.

  
  

  - If it gives a straight line, you can use the one-compartment model.