Phenobarbital Case #3

Date: 5/18/95
Name: Yukon
Signalment: Canine, Male, 10 yrs, 88 pounds
History:Epileptic for 7-8 years -- last 2 weeks has break through seizures and liver enzymes are elevated
Current Status: Seizures are occurring more often -- 2 last Wednesday
Dose:180 mg, PO Dose Interval: 12 h
Time on Dose:1 year
Serum Concentration #1: 48.4 ug/mL @ 3 h #2: none submitted

Graphing the data

• Plot data from case on arithmetic graph paper
  • May use same graph as did for Case #1 & 2, if wish
  • make "y" axis 0 to 50 (mcg/mL serum)
  • make "x" axis 0 to 14 (hours)
  • plot concentration #1 (48.4 mcg/mL @ 3 h)
  • Note there is no sample #2

Question

• Is this value closer to the "peak" or to the "trough"?
  On what do you base this estimate?
• Will the concentration go lower during this dose interval?
  Given what you know about the speed at which phenobarbital is eliminated what is your prediction about how much lower?
• How was this sample time probably chosen?
• Is it ideal? ...practical?
• Will it introduce significant error in dose adjustment?

Questions regarding the significance of the data

• The concentration is approximately 48.4 mcg/mL at 3 hours ... So what?
• Is the concentration within the target concentration range?
• Is "Yukon" still having seizures?

Adjust regimen

• Normally recommended maximum concentration is 40 mcg/mL
• Should the dose be decreased for Yukon?
• If yes, use same proportion as before, BUT...
• Setup simple proportion formula
  

  New dose = Old dose x (Conc desired / Conc measured)

• Do the calculation

Questions about adjusting regimen

• What is rationale for decreasing the dose?
• What is the probability that phenobarbital alone (at tolerable doses) will ever stop the seizures in Yukon?
• How important would it have been to know the trough concentration in this case?

Advice to referring veterinarian

Concentration at "peak" (48.4 mcg/mL) is clearly above the maximum recommended level of 40 mcg/mL. Because the seizures are not being controlled at this dosage and because the liver enzymes are already elevated (a sign of potential hepatotoxicity), it is unlikely that phenobarbital will be satisfactory as a sole agent. Advise considering reducing dosage by 1/3 and adding KBr to the regimen.