Module 9. Relationship between volume of distribution and clearance. Effect of volume of distribution (only) changes.

Objectives

Having completed this exercise and based on pharmacokinetic constants and data, students should be able to:

Significance

S.L. Green et. al.: Effects of hypoxia and azotaemia on the pharmacokinetics of amikacin in neonatal foals. Equine Veterinary J. 24(6), 475-479, 1992.

Gram-negative septicemia in the newborn foal is a major cause of neonatal mortality. Aminoglycoside antibiotics are an excellent choice for treatment or prevention of gram negative sepsis. However, aminoglycoside pharmacokinetics are different in foals than in adult horses. Consequently, it is important to make appropriate dose and interval corrections in order to provide safe and effective therapy. Especially in foals, it is possible to produce aminoglycoside toxicity without producing bactericidal aminoglycoside therapy!

Exercise

Download amikacinvolume.xlsx, the spreadsheet for this exercise. Depending on your settings, you may have to "enable editing" in order to make the changes suggested by the exercise.

Pharmacokinetic variables on the worksheet are preset for amikacin in horses.

Target concentrations

Manipulate the dosage

Inspect

Calculated values

Steady-State Concentrations (for repeated doses during therapy).

Graphs

Assess

Questions (Key)

  1. List the most (clinically) important differences in calculated values between adults and foals.
  2. What general recommendations can be made for the proper dose and interval of aminoglycosides given to neonatal foals?
  3. Examine the plot of the plasma concentration profile for the foal after you make your final dose adjustment. The plasma concentrations are below MIC for typical sensitive organisms (2.0 - 3.0 μg/ml) for about 6 hours out of each dose interval. What could you do for this patient to provide continuous antimicrobial therapy without risking gentamicin intoxication? (It should be clear that changing doses and intervals of gentamicin will not work. You need to think outside the pharmacokinetic box.)