Pharmacokinetics, nephrotoxicosis, and in vitro antibacterial activity associated with single versus multiple (three times) daily gentamicin treatments in horses

Leanne M. Godber From the Departments of Large Animal Clinical Sciences (Godber, Derksen), Microbiology (Walker), and Small Animal Clinical Sciences (Hauptman), College of Veterinary Medicine, and the Department of Medicine, College of Medicine (Stein), Michigan State University, East Lansing, MI 48824.

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Robert D. Walker From the Departments of Large Animal Clinical Sciences (Godber, Derksen), Microbiology (Walker), and Small Animal Clinical Sciences (Hauptman), College of Veterinary Medicine, and the Department of Medicine, College of Medicine (Stein), Michigan State University, East Lansing, MI 48824.

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Gary E. Stein From the Departments of Large Animal Clinical Sciences (Godber, Derksen), Microbiology (Walker), and Small Animal Clinical Sciences (Hauptman), College of Veterinary Medicine, and the Department of Medicine, College of Medicine (Stein), Michigan State University, East Lansing, MI 48824.

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Joe G. Hauptman From the Departments of Large Animal Clinical Sciences (Godber, Derksen), Microbiology (Walker), and Small Animal Clinical Sciences (Hauptman), College of Veterinary Medicine, and the Department of Medicine, College of Medicine (Stein), Michigan State University, East Lansing, MI 48824.

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 DVM, MS
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Frederik J. Derksen From the Departments of Large Animal Clinical Sciences (Godber, Derksen), Microbiology (Walker), and Small Animal Clinical Sciences (Hauptman), College of Veterinary Medicine, and the Department of Medicine, College of Medicine (Stein), Michigan State University, East Lansing, MI 48824.

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 DVM, PhD

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SUMMARY

Once-daily administration of aminoglycosides may be a safe and effective therapeutic regimen, on the basis of the microbiologic and pharmacokinetic characteristics of these antibiotics. This study was designed to determine serum and tissue concentrations following IV administration of gentamicin, at dosages of 6.6 mg/kg of body weight, every 24 hours, and 2.2 mg/kg, every 8 hours, for 10 days in adult horses. Nephrotoxicosis from these dosage regimens also was compared, and microbiologic effects, including postantibiotic effects, were determined with various concentrations of gentamicin against an equine clinical isolate of Pseudomonas aeruginosa. Treatment at the 6.6-mg/kg dosage resulted in maximal serum concentrations (77.93 ± 19.90 μg/ml, mean ± sem) and area under the concentration-vs-time curves (83.79 ± 14.97 μg.h/ml) that were significantly (P < 0.05) greater than those following treatment at the 2.2-mg/kg dosage (5.05 ± 0.50 μg/ml and 6.03 ± 0.66 μg.h/ml, respectively). Nephrotoxicosis was not induced with either dosage regimen, and postantibiotic effects were prolonged with a higher gentamicin concentration. This study provided evidence to support the use of once-daily gentamicin treatment in adult horses.

SUMMARY

Once-daily administration of aminoglycosides may be a safe and effective therapeutic regimen, on the basis of the microbiologic and pharmacokinetic characteristics of these antibiotics. This study was designed to determine serum and tissue concentrations following IV administration of gentamicin, at dosages of 6.6 mg/kg of body weight, every 24 hours, and 2.2 mg/kg, every 8 hours, for 10 days in adult horses. Nephrotoxicosis from these dosage regimens also was compared, and microbiologic effects, including postantibiotic effects, were determined with various concentrations of gentamicin against an equine clinical isolate of Pseudomonas aeruginosa. Treatment at the 6.6-mg/kg dosage resulted in maximal serum concentrations (77.93 ± 19.90 μg/ml, mean ± sem) and area under the concentration-vs-time curves (83.79 ± 14.97 μg.h/ml) that were significantly (P < 0.05) greater than those following treatment at the 2.2-mg/kg dosage (5.05 ± 0.50 μg/ml and 6.03 ± 0.66 μg.h/ml, respectively). Nephrotoxicosis was not induced with either dosage regimen, and postantibiotic effects were prolonged with a higher gentamicin concentration. This study provided evidence to support the use of once-daily gentamicin treatment in adult horses.

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