Kineticlass - Dose rate of Chloramphenicol in Dogs and Cats

ProbIIb Header

Dosing (Cats are not little dogs)

KinetiClass (IIa)

Concepts

Dose rate
Cave (average plasma concentrations)
Species differences in pharmacokinetics (Cats are not small dogs).

Reference
A.D.J. Watson: Oral Chloramphenicol dosage regimens in cats. J. Veterinary Pharmacology and Therapeutics. 3 (145-149), 1980.

Significance
Early dose recommendations for Chloramphenicol administration in cats suggested that cats should be treated as small dogs (same 50 mg/kg dose, same 8 hour dose interval). Given in this fashion, Chloramphenicol produces more side effects (depressed white cell count, anorexia, etc.) in cats than dogs. The recommended cat dosage is 25 mg/kg q12H. The therapeutic (safe and effective) concentration range for Chloramphenicol (all species?) is 5 - 15 µg/ml.

Exercise

1) Pharmacokinetic variables on the spreadsheet are preset for a typical cat given Chloramphenicol.

2) Both simulations

Set Lower (Minimum effective concentration) to 5
Set Upper (Minimum Toxic concentration) to 15.

3) Simulation #1 (Recommended dosing for cats).

Set the dose to 25 mg/kg
Set the weight to any reasonable cat weight
Set the interval to 12.

4) Simulation #2 (Recommended dosing for dogs).

Set the dose to 50 mg/kg
Set the weight to any reasonable cat weight
Set the interval to 8.

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

6) Review the graph of the simulations. Pay particular attention to whether the plasma concentration exceed the toxic concentration and what portion of the time each spends above the effective concentration.

Questions

Questions:

1) Calculate the dose rate for each simulation.

2) Describe the difference between the two dose regimes in average plasma concentration? peak concentration? minimum concentration?

3) What portion of time (during each dose interval) are effective concentrations maintained if the dog dosage is used?, if the cat dosage is used?

4) Which dose regimen is more likely to produce efficacy? (Remember that efficacy and toxicity are independent for chloramphenicol. It may be that chloramphenicol MIGHT inhibit the bacteria and kill the cat.)

5) What portion of time (during each dose interval) are toxic concentrations exceeded if the dog dosage is used?, if the cat dosage is used?

6) Which dosage is more likely to produce toxicity?

7) What is the primary reason (mechanism, not pharmacokinetic constant) for the increased sensitivity of cats to Chloramphenicol?