PHARMACOKINETICS, NEPHROTOXICOSIS, AND IN-VITRO ANTIBACTERIAL ACTIVITY ASSOCIATED WITH SINGLE VERSUS MULTIPLE (3 TIMES) DAILY GENTAMICIN TREATMENTS IN HORSES

Once-daily administration of aminoglycosides may be a safe and effecti ve therapeutic regimen, on the basis of the microbiologic and pharmaco kinetic characteristics of these antibiotics. This study was designed to determine serum and tissue concentrations following rv administrati on of gentamicin, at dosages of 6.6 mg/kg of body weight, every 24 hou rs, and 2.2 mg/kg, every 8 hours, for 10 days in adult horses. Nephrot oxicosis from these dosage regimens also was compared, and microbiolog ic effects, including postantibiotic effects, were determined with var ious concentrations of gentamicin against an equine clinical isolate o f Pseudomonas aeruginosa. Treatment at the 6.6-mg/kg dosage resulted i n maximal serum concentrations (77.93 +/- 19.90 mu g/ml, mean +/- SEM) and area under the concentration-vs-time curves (83.79 +/- 14.97 mu g . h/ml) that were significantly (P < 0.05) greater than those followi ng treatment at the 2.2-mg/ kg dosage (5.05 +/- 0.50 mu g/ml and 6.03 +/- 0.66 mu g . h/ml, respectively). Nephrotoxicosis was not induced w ith either dosage regimen, and postantibiotic effects were prolonged w ith a higher gentamicin concentration. This study provided evidence to support the use of once-daily gentamicin treatment in adult horses.