title: Pharmacokinetics, nephrotoxicosis, and in vitro antibacterial activity associated with single versus multiple (three times) daily gentamicin treatments in horses.
abstract: 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 i.v. 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 micrograms/ml, mean +/- SEM) and area under the concentration-vs-time curves (83.79 +/- 14.97 micrograms.h/ml) that were significantly (P < 0.05) greater than those following treatment at the 2.2-mg/kg dosage (5.05 +/- 0.50 micrograms/ml and 6.03 +/- 0.66 micrograms.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.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Godber
authors.forename: R D
authors.initials: RD
authors.lastname: Walker
authors.forename: G E
authors.initials: GE
authors.lastname: Stein
authors.forename: J G
authors.initials: JG
authors.lastname: Hauptman
authors.forename: F J
authors.initials: FJ
authors.lastname: Derksen
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005839:Gentamicins / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D007674:Kidney Diseases / Q000139:chemically induced / Q000662:veterinary*; D008297:Male; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects
chemical_list: D005839:Gentamicins