title: Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses.
abstract: The aim of this study was to determine the pharmacokinetics of amikacin and penicillin G sodium when administered in combination as an intravenous regional limb perfusion (IVRLP) to horses. Seven healthy adult horses underwent an IVRLP in the cephalic vein with 2 g of amikacin sulfate and 10 mill IU of penicillin G sodium diluted to 60 mL in 0.9% saline. A pneumatic tourniquet set at 450 mmHg was left in place for 30 min. Synovial fluid was collected from the metacarpophalangeal joint 35 min and 2, 6, 12, and 24 h after infusion of the antimicrobials. Concentrations of amikacin and penicillin in synovial fluid were quantitated by liquid chromatography tandem-mass spectrometry analysis. Therapeutic concentrations of amikacin and penicillin for equine-susceptible pathogens were achieved in the synovial fluid. Maximum synovial concentrations (Cmax) (mean ± SE) for amikacin and penicillin were 132 ± 33 μg/mL and 8474 ± 5710 ng/mL, respectively. Only 3 horses had detectable levels of penicillin at 6 h and 1 at the 12 h sample. The combination of amikacin with penicillin G sodium via IVDLP resulted in reported therapeutic concentrations of both antibiotics in the synovial fluid. The Cmax:MIC (minimum inhibitory concentration) ratio for amikacin was 8:1 and Time > MIC for penicillin was 6 h. At 24 h, the mean concentration of amikacin was still above 4 μg/mL. Terminal elimination rate constants (T1/2 lambdaz) were 13.6 h and 2.8 h for amikacin and penicillin, respectively. The use of IVDLP with penicillin may therefore not be practical as rapid clearance of penicillin from the synovial fluid requires frequent perfusions to maintain acceptable therapeutic concentrations.
authors.affiliation: Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Nieto
authors.affiliation: Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Trela
authors.affiliation: Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Stanley
authors.affiliation: Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
authors.forename: Sawsan
authors.initials: S
authors.lastname: Yamout
authors.affiliation: Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
authors.forename: Jack R
authors.initials: JR
authors.lastname: Snyder
mesh_terms: D061605:Administration, Intravenous; D000583:Amikacin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D008297:Male; D010400:Penicillin G / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010477:Perfusion / Q000662:veterinary; D013582:Synovial Fluid / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D000583:Amikacin; D010400:Penicillin G