Concepts

Reference
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.

Significance
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

1) Pharmacokinetic variables on the spreadsheet for simulation #1 are preset for a normal cat (N) given gentamicin, simulations #2, #3, and #4 are preset for a cat with renal disease (RD) given gentamicin.

2)Review the calculated values at the bottom of the worksheet.

3) Review the top graph to compare the consequences of normal dosing in a normal cat (#1) and in a cat with renal failure (#2).

4) Dose adjustment method

• Set the dose for simulation 1 to 0.0 to get it out of your way.
• Gradually adjust the dose for the renal disease patient #3 so that the minimum concentration (Cmin) is < 1.0 µg/ml.

5) Interval adjustment method.

• Adjust the interval for the renal disease patient #4 so that the minimum concentration (Cmin) is < 1.0 µg/ml.

6) Compare the top graph (#1 and #2) to the bottom graph (#3 and #4) and assess the consequences of your dose regimen adjustments.

Questions:

1) In order to avoid toxicity, concentrations of gentamicin must fall to at least 1.0 µg/ml at the end of each dose interval. Which method, lower dose (#3) vs. extended interval (#4), is appropriate for dose adjustment of gentamicin in a patient with moderate renal dysfunction?

2) Why is it inappropriate to (only) reduce the dose of gentamicin to avoid toxicity in a renal failure patient? By the way, renal failure (the disease process) may also affect the volume of distribution (probably decreased) and the absorption rate (probably decreased) in the clinical setting.

3) Using simulation #4, answer the following questions: If gentamicin concentrations must exceed 3.0 µg/ml to inhibit the growth of bacteria (MIC = 3.0), how many hours of effective therapy do you provide each day? For how many hours are concentrations less than effective?