Case #2 -- Gentamicin

 Date: 5/24/95
Name: John Doe
Signalment: male, 50 kg
History: Weak, transfusion 5/23/95
Current Status:improving
Dose: 4 mg/kg IV Dose Interval: 8 h
Time on Dose:since 5/22/95 at 8 PM
Serum Concentration #1: 5.0 mcg/mL @ 1 h #2: 0.9 mcg/mL @ 8 h

Graphing the data

• Plot data from case on arithmetic graph paper
  • make "y" axis 0 to 20 (mcg/mL serum)
  • make "x" axis 0 to 14 (hours)
  • Plot concentration #1 (5.0 mcg/mL @ 1 h)
  • Plot concentration #2 (0.9 mcg/mL @ 8h )

Questions about the graph

• Is this the highest the concentration is likely to be (or have been) during this dose interval?
• Will the concentration go lower during this dose interval?
• Draw your idea of what might the "curve" look like if one had all the data?
• Does the concentration change much during the dose interval?
• What does this change indicate about the "rate of elimination" -- fast? slow?
  Note contrast relative to anticonvulsant example
• Is this a first time dose? Can one tell?
• How were sample times probably chosen?
• What fluid was measured? Why?

Questions regarding the significance of the data

• The concentration is approximately 5 mcg/mL @ 1 hour, ... So what?
• The concentration is approximately 0.88 mcg/mL @ 8 hours, ... So what?
• How does the ratio of trough to peak compare to that in the anticonvulsant example?

Review of therapeutic window

• Draw horizontal lines across graph at --
  • 12 mcg/mL
  • 5 mcg/mL
  • 1 mcg/mL
• Write "often toxic" above the 12 mcg/mL line, the MTC
• Write "insufficient effect" below the 5 mcg/mL line, the MEC
• Write "need to drop below" below the 1 mcg/mL line, (another MTC?)

Questions about "therapeutic window"

• Where is the therapeutic window in this graph?
• What is the meaning of the "need to drop below" statement
• How might his relate to toxicity of gentamicin
• Are these concentrations "absolute"?
• Note: this is the traditional understanding of ideal gentamicin dosage regimens. New concepts will be presented in the chemotherapeutic section.

Evaluation of the regimen

• Look at the observed concentrations in this case vis-a-vis the therapeutic window
• Note that the Mr. Doe was said to be "improving" -- What does this mean for advising physician?

Questions about the dose regimen

• Should one change the dose and/or schedule for Mr. Doe?
• Why or why not?