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Depenbrock MS Thesis 4 15 15.pdf (2.84 MB)

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Pharmacokinetics of Ampicillin-Sulbactam in Serum and Synovial Fluid Samples Following Regional Intravenous Administration in the Distal Hind Limb of Adult Cattle

Depenbrock, Sarah Marie
http://rave.ohiolink.edu/etdc/view?acc_num=osu1429107883

Abstract Details

2015, Master of Science, Ohio State University, Comparative and Veterinary Medicine.
Objective: The goal of this study was to define the pharmacokinetics of ampicillin-sulbactam in synovial fluid and serum of the digital circulation and central venous circulation following administration as a regional intravenous limb perfusion (RLP) of the distal hind limb in cattle. Animals: Six healthy, adult, non-lactating dairy cows with no evidence of digital infection or lameness. Procedures: Intravenous catheters were placed in the dorsal common digital vein (DCDV) of the right hind limb and in the jugular vein; an indwelling catheter was placed in the metatarsophalangeal joint of the right hind limb in all animals. An RLP of the distal extremity was performed using a tourniquet applied at the proximal metatarsus and 1.5 g combined ampicillin-sulbactam (1g ampicillin, 0.5g sulbactam) was administered into the DCDV. Synovial fluid was collected from the metatarsophalangeal joint, and blood was collected from the DCDV and jugular vein at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 18, and 24 hours post infusion. A single blood sample was taken from the abaxial proper plantar vein (APPV) of the lateral digit of the right hind limb at 0.25 hours post-perfusion. Synovial fluid and serum were analyzed by high-pressure liquid chromatography (HPLC). Results: Maximum mean concentration of ampicillin in synovial fluid, DCDV, APPV and systemic circulation (+ St. Dev) were 1995 (+1011), 4827 (+ 1883), 5423 (+ 1953) and 2.5 (+ 1.6) µg/mL respectively. Sulbactam concentrations followed similar trends to ampicillin concentrations, and sulbactam concentrations remained near half ampicillin concentrations, and above during the later time points. The best fit line for the mean concentration of ampicillin in synovial fluid dropped below 8µg/mL (the CLSI breakpoint MIC for ampicillin) at 18.9 (range 15.4-24.9) hours after RLP. No adverse events were encountered throughout the duration of the study or following removal of the catheters. Conclusions and Clinical Relevance: Both drugs reached high concentrations in digital circulation and synovial fluid of the distal limb, but central venous blood concentrations remained low. Ampicillin concentrations remain above therapeutic concentrations for common organisms in synovial fluid for greater than 80% of a 24 hour period, without a relative decrease in sulbactam, suggesting that once daily dosing as an RLP may be sufficient to provide therapeutic concentrations to synovial structures of the bovine distal limb. Further research is needed to assess treatment efficacy in cattle clinically affected by digital infections, including deep digital sepsis.
Katharine Simpson (Advisor)
Jeff Lakritz (Committee Member)
Andrew Niehaus (Committee Member)
78 p.
Veterinary Services
Bovine, Foot, Extremity, Sepsis,

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Citations

  • Depenbrock, S. M. (2015). Pharmacokinetics of Ampicillin-Sulbactam in Serum and Synovial Fluid Samples Following Regional Intravenous Administration in the Distal Hind Limb of Adult Cattle [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429107883

    APA Style (7th edition)

  • Depenbrock, Sarah. Pharmacokinetics of Ampicillin-Sulbactam in Serum and Synovial Fluid Samples Following Regional Intravenous Administration in the Distal Hind Limb of Adult Cattle. 2015. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1429107883.

    MLA Style (8th edition)

  • Depenbrock, Sarah. "Pharmacokinetics of Ampicillin-Sulbactam in Serum and Synovial Fluid Samples Following Regional Intravenous Administration in the Distal Hind Limb of Adult Cattle." Master's thesis, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429107883

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.
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