title: The disposition of five therapeutically important antimicrobial agents in llamas.
abstract: The disposition of five therapeutic antimicrobial agents was studied in llamas (Lama glama) following intravenous bolus administration. Six llamas were each given ampicillin, tobramycin, trimethoprim, sulfamethoxazole, enrofloxacin and ceftiofur at a dose of 12 mg/kg, 1 mg/kg, 3 mg/kg, 15 mg/kg, 5 mg/kg, and 2.2 mg/kg of body weight, respectively, with a wash out period of at least 3 days between treatments. Plasma concentrations of these antimicrobial agents over 12 h following i.v. bolus dosing were determined by reverse phase HPLC. Disposition of the five antimicrobial agents was described by a two compartment open model with elimination from the central compartment, and also by non-compartmental methods. From compartmental analysis, the elimination rate constant, half-life, and apparent volume of distribution in the central compartment were determined. Statistical moment theory was used to determine noncompartmental pharmacokinetic parameters of mean residence time, clearance, and volume of distribution at steady state. Based on the disposition parameters determined, and stated assumptions of likely effective minimum inhibitory concentrations (MIC) a dose and dosing interval for each of five antimicrobial agents were suggested as 6 mg/kg every 12 h for ampicillin; 4 mg/kg once a day or 0.75 mg/kg every 8 h for tobramycin; 3.0 mg/kg/15 mg/kg every 12 h for trimethoprim/sulfamethoxazole; 5 mg/kg every 12 h for enrofloxacin; and 2.2 mg/kg every 12 h for ceftiofur sodium for llamas. Steady-state peak and trough plasma concentrations were also predicted for the drugs in this study for llamas.
authors.affiliation: College of Pharmacy, Oregon State University, Corvallis 97331-3507, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Christensen
authors.forename: B B
authors.initials: BB
authors.lastname: Smith
authors.forename: S B
authors.initials: SB
authors.lastname: Murdane
authors.forename: N
authors.initials: N
authors.lastname: Hollingshead
mesh_terms: D000667:Ampicillin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D002161:Camelids, New World; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose; D004350:Drug Residues / Q000378:metabolism / Q000493:pharmacokinetics*; D000077422:Enrofloxacin; D024841:Fluoroquinolones; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D010406:Penicillins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D012984:Software; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014031:Tobramycin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D014295:Trimethoprim / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; D010406:Penicillins; D015363:Quinolones; D000077422:Enrofloxacin; D000667:Ampicillin; C053503:ceftiofur; D014295:Trimethoprim; D013420:Sulfamethoxazole; D014031:Tobramycin