Pharmacokinetics 6

Question 1

Relationship of T_1/2, Vd, and CL

Answer 1

• The half-life is inversely proportional to clearance
  
  • if the CL decreases, the T_1/2 increases proportionally
• The half-life is proportional to the volume of distribution
  
  • If the Vd increases, T_1/2 increases proportionally

Question 2

Area Under the Curve (AUC)

Answer 2

• Represents total drug exposure (concentration and duration)
• Units:
  
  • (x-axis)*(y-axis)
  • hr*mcg/ml
• Most commonly proportional to dose
  
  • Double the dose, double the area under hte curve
  • Half the dose, half the area under the curve
• Effects of organ failure/dysfunction
  
  • if the half-life doubles the AUC doubles (in the body longer)
• Effects of Metabolism Induction
  
  • if the half-life decreases by 50%, the AUC decreases by 50%

Question 3

AUC - Utility:

Theraputic efficacy

Answer 3

Clinical efficacy is correlated to the ratio of the AUC to the Minimum Inhibitory Concentration (MIC) of the bacteria treated

MIC = lowest dose that inhibits bacteria

Question 4

AUC - utility:

Drug Toxicity

Answer 4

As cumulative AUC increases for aminoglycosides, the risk of nephrotoxicity increases

Longer patient is on the drug

Question 5

AUC - Utility:

Bioavailability

Answer 5

(Fraction of the dose absorbed)

THe extent of systemic drug absorption following non-IV dosing

Question 6

AUC - Utility:

Bioequivalent

Answer 6

Are two different drug formulations equivalent?

Generic vs. Brand name

AUC and Cmax

Question 7

Bioavailability VS. absorption

Answer 7

Factors affecting Bioavailability

1. Not absorbed:
   
   1. unable to diffuse
   2. IM flunixin, SQ penG in cattle
2. First pass metabolism
   
   1. may be completely absorbed, but metabolized prior to reaching systemic circulation

Question 8

Maximum Plasma Concentration (Cmax) and Time to Cmax (Tmax)

Answer 8

• Cmax should change proportional to dose
  
  • Dose is doubled, Cmax is doubled
  • DOse half, Cmax half
• Tmax should NOT change with dose
  
  • should be constant, no saturation

Question 9

Constant Rate Infusion (CRI)

Answer 9

Purpose

• Maintain steady plasma concentrations
• Minimize fluctuations in plasma concentrations

Parameters:

• Css - concentration to steady state
• Ro - rate of drug administration
• Cl - total body clearance
• Ro = Css * Cl
  *

Question 10

Steady State Plasma Concentration (Css)

Answer 10

Time to steady state plasma concentration = 5 half-lives

True regardless of the drug, dose, and dose interval

Similar to the elimination of drugs

Question 11

Loading Dose

Answer 11

• Administered to rapidly achieve plasma concentrations
• Important for drugs with long T_1/2 or those in which you need an immediate effect
• D = Cp*Vd
  *