Module 10. Effect of dysfunction of an organ of elimination on pharmacokinetics.

Objectives

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

Significance

Frazier DL; Aucoin DP; Riviere JE: Gentamicin pharmacokinetics and nephrotoxicity in naturally acquired and experimentally induced disease in dogs. J Am Vet Med Assoc (HAV), 1988 Jan 1; 192 (1): 57-63.

Occasionally (geriatric animal that acquires an infection while on adequate doses of enrofloxacin) it is necessary to use aminoglycoside antibiotics in the presence of renal dysfunction. It is important that appropriate doses and intervals are used in order to produce safe and effective therapy.

Exercise

Download gentamicinrenalfailure.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 four dogs with different degrees of renal dysfunction. The patients approximate:

Doses for simulations 2-4 are set to 0(zero) to allow you to reveal graphical and steady-state results one simulation at a time:

Target concentrations

Manipulate the dosage

Inspect

Calculated values

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

Graphs

Assess

Questions (Key)

  1. Describe the concentration profile for simulation #2 (3.3 mg/kg q8H in terms of efficacy and toxicity).
  2. Describe the concentration profile for simulation #3 (9.9 mg/kg q24H) in terms of efficacy and toxicity.
  3. Describe the concentration profile for simulation #4 (9.9 mg/kg q24H) interms of efficacy and toxicity.
  4. In terms of its pharmacokinetic profile, how is a renal failure patient different from the neonatal patient that you studied in exercise IIe?