title: Single and multiple dose pharmacokinetics of gentamicin administered intravenously and intramuscularly in adult conditioned thoroughbred mares.
abstract: The pharmacokinetics of gentamicin following single and multiple intravenous and intramuscular doses were compared in a two phase, randomised cross-over study in horses. Gentamicin was administered to 6 healthy, conditioned Thoroughbred mares at a dosage of 3.3 mg/kg body weight every 12 hours for 5 intravenous or intramuscular consecutive treatments. Equal numbers of horses were treated by either route during each phase. There was a wash-out period of 5 days between phases. During each phase serial blood samples were collected from each mare immediately before treatment and at 16 intervals following the first and fifth administrations. Blood samples were also collected immediately before treatment and at 30 and 60 minutes following doses 2 through to 4. Gentamicin plasma concentrations were determined by fluorescence polarisation immunoassay. Plasma gentamicin concentration versus time data for both single and multiple doses by either route was best described by a 2 compartmental open model with first order rate constants. A distribution half-life (T1/2 alpha) of 0.1 +/- 0.1 hours, terminal half-life (T1/2 beta) of 1.2 +/- 0.2 hours, mean residence time (MRT) of 1.4 +/- 0.1 hours and total body clearance (ClB) of 1.4 +/- 0.2 ml/kg/min were observed following multidose gentamicin intravenous administration. The volume of distribution at steady state (Vdss) was 117.6 +/- 10.8 ml/kg. No significant differences (P > 0.05) were observed for any of the parameters between single or multiple doses for either route of administration. Except for AUC, significant (P < or = 0.05) differences were observed between multiple intravenous and intramuscular treatments for all pharmacokinetic parameters determined.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Republic of South Africa.
authors.forename: G E
authors.initials: GE
authors.lastname: Swan
authors.forename: A J
authors.initials: AJ
authors.lastname: Guthrie
authors.forename: M S
authors.initials: MS
authors.lastname: Mülders
authors.forename: V M
authors.initials: VM
authors.lastname: Killeen
authors.forename: J P
authors.initials: JP
authors.lastname: Nurton
authors.forename: C R
authors.initials: CR
authors.lastname: Short
authors.forename: J S
authors.initials: JS
authors.lastname: van den Berg
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D005839:Gentamicins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006736:Horses / Q000097:blood*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins