Case 6 Aminoglycoside and intensive fluid therapy Signalment:  Two year old male intact Staffordshire Terrier Chief Complaint:  Peritonitis and bacteremia secondary to prostatic abscess Pertinent History:  Surgical correction of prostatic abscess. Drug samples collected 24 hours postoperatively. Other Drugs:  Antiemetics (metoclopramide); intensive fluid therapy (balanced crystalloid) Drug of Interest:  Gentamicin Concern:  Efficacy and safety Dosing Regimen:  4 mg/kg IV every 24 hours Duration of Current Regimen:  24 hours Patient Response:  Febrile, non-responsive Drug Concentration: 5.34 mg/ml     Time: 2 hours (peak) 0.73 mg/ml     Time: 9 hours Drug Elimination Half-Life:  2.4 hrs Volume of Distribution:  0.45 l/kg Predicted Peak Concentration:  10 mg/ml Trough Concentration:  Nnon-detectable Recommendation:  Double the dose to target 20 mg/ml (assuming an MIC of 1 to 2 mg/ml) and maintain current 24 hour dosing interval. Follow-Up:  Patient condition remained critical for two more postoperative days but then began progressive improvement. Patient was discharged 10 days post-operatively. Comments:  Peak gentamicin concentration was lower than expected (expected: 10 mg/ml), presumably due to intensive fluid therapy. The reported volume of distribution for gentamicin in dogs is 0.25 l/kg, but was 0.45 l/kg in this patient. Gentamicin is distributed to extracellular fluid, which was probably increased in this patient by fluid therapy. A nearly doubled distribution volume resulted in a near halving of peak concentrations. The drug elimination half-life in this patient is 2.4 hours, which is normal. Doubling of the dose will add only one drug half-life to the time that target trough concentrations (<1 mg/ml) will be reached, which currently occurs by 9 hours in this patient. Even if the drug elimination half-life were to double (to 5 hours), sufficient time will elapse during a 24 hour dosing interval to allow drug concentrations to reach the targeted 1 mg/ml. Note that the trough sample was not collected in this patient just prior to the next dose (i.e., at 24 hours). Drug would not have been detectable at that time, hence trough concentrations were collected after 2 predicted drug half-lives had elapsed. [back to top]