Phenobarbital Case #1

Date: 5/16/95
Name: Kissie
Signalment: Canine, Female, 11 yrs, 12 pounds
History: Seizures started 12/94. Medications started 4/95. Chemistry panel normal
Current Status: No seizures since started current dose regimen
Dose: 12 mg (elixir), PO Dose Interval: 12 h
Time on Dose:3 weeks
Serum Concentration #1: 20.2 mcg/mL @ 2 h #2: 19.9 mcg/mL @ 12 h 

Graphing the data

• Plot data from case on arithmetic graph paper
  • make "y" axis 0 to 50 (mcg/mL serum)
  • make "x" axis 0 to 14 (hours)
  • Plot 2 hr concentration = 20.2 mcg/mL
  • Plot 12 hr concentration = 19.9 mcg/mL

Questions about graph

• What fluid was measured? Why?
• How were sample times chosen?
• Does the concentration change much during the dose interval?
• During this dose interval, will the concentration more than likely go | higher | lower | than the reported values?
• What might the "curve" look like if one had all the data?
  Draw a light dotted line representing your notion of the curve's shape
• Given the two concentrations and sample times, predict whether this drug is eliminated | rapidly or slowly |.
• [scan ] What you should have produced
• [drawing][scan] Graph of phenobarbital concentration versus time
  (scan is figure 1, Ravis et al, AJVR 45:1283-1286, 1984)

Questions regarding the significance of the data

• The concentration is approximately 20.2 ug/mL at 2 hours ... So what?
• The concentration is approximately 19.9 ... So what?
• How does serum/plasma drug concentration relate to effect?
• Procainamide concentration vs effect (Koch-Weser73: , 5th Int. Cong. Pharmacol. Pharmacology and Future of Man. Problems of Therapy, Vol. 3, 1973)

Areas of the graph

• Draw two heavy horizontal lines across graph --
  one at 20 ug/mL -- Label it Minimum Effective Concentration (MEC)
  one at 40 ug/mL -- Label it Minimum Toxic Concentration (MTC)
• Write "often toxic" above the 40 ug/mL line
• Write "insufficient effect" below the 20 ug/mL line

Questions about areas of the graph

• What name might one give to the "middle" area of the graph?
• How might one establish the "minimum toxic" and "minimum effective" concentrations?
• Are these concentrations "absolute"?

Evaluation of the regimen

• Look at the observed concentrations in this case vis-a-vis the therapeutic window you have made
• Note that the "Kissie" has not had seizures for 3 weeks

Questions about the dose regimen

• Should one change the dose and/or schedule for Kissie?
• Why or why not?