Drug disposition and dosage determination of once daily administration of gentamicin sulfate in horses after abdominal surgery

Abstract

Objective - To evaluate pharmacokinetics of once daily IV administration of gentamicin sulfate to adult horses that had abdominal surgery. Design - Prospective study. Animals - 28 adult horses that underwent abdominal surgery for colic. Procedure - 14 horses were treated with each dosage of gentamicin (ie, 6.6 or 4 mg/kg, IV, q 24 h) and blood samples were collected for pharmacokinetic analysis. Plasma gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. Pharmacokinetic analysis measured the elimination half-life, volume of distribution, and gentamicin total systemic clearance. Treatment outcome, CBC, and serum creatinine concentrations were recorded. Results - 1 horse in the high-dosage group died. All other horses successfully recovered, and did not develop bacterial infection or have evidence of drug toxicosis resulting in renal injury. Mean pharmacokinetic variables for gentamicin administration at a high or low dosage (ie, 6.6 or 4 mg/kg, IV, q 24 h) were half-life of 1.47 and 1.61 hours, volume of distribution of 0.17 and 0.17 L/kg, and systemic clearance of 1.27 and 1.2 ml/kg/min, respectively. Mean serum creatinine concentration was 1.74 and 1.71 for the high and low dosages, respectively, and serum creatinine concentration was not correlated with gentamicin clearance. Conclusions and Clinical Relevance - Gentamicin administration at a dosage of 4 mg/kg, IV, every 24 hours, will result in plasma concentrations that are adequate against susceptible bacteria with a minimum inhibitory concentration (MIC) of ≤ 2.0 μg/ml. Gentamicin administration at a calculated dosage of 6.8 mg/kg, IV, every 24 hours will result in optimum plasma concentrations against susceptible bacteria with a MIC of ≤ 4.0 μg/ml.