Tarsocrural joint polymyxin B concentrations achieved following intravenous regional limb perfusion of the drug via a saphenous vein to healthy standing horses

Robert T. Snowden 1Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996.

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James Schumacher 1Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996.

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James T. Blackford 1Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996.

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Ellie E. Cypher 1Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996.

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Sherry K. Cox 2Department of Biomedical and Diagnostic Services, University of Tennessee, Knoxville, TN 37996.

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Xiaocun Sun 3College of Veterinary Medicine, and the Department of Research Computing Support, Office of Information and Technology, University of Tennessee, Knoxville, TN 37996.

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Brian K. Whitlock 1Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996.

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Abstract

OBJECTIVE

To determine whether therapeutic concentrations (> 0.5 to 1.0 μg/mL) of polymyxin B (PB) were achieved in the tarsocrural joint of horses when the drug was administered by IV regional limb perfusion (IV-RLP) via a saphenous vein at doses of 25, 50, and 300 mg and to describe any adverse systemic or local effects associated with such administration.

ANIMALS

9 healthy adult horses.

PROCEDURES

In the first of 2 experiments, 6 horses each received 25 and 50 mg of PB by IV-RLP via a saphenous vein with at least 2 weeks between treatments. For each treatment, a tourniquet was placed at the midmetatarsus and another was placed midway between the stifle joint and tarsus. Both tourniquets were removed 30 minutes after the assigned dose was administered. Blood and tarsocrural joint fluid samples were collected for determination of PB concentration before and at predetermined times after drug administration. In experiment 2, 4 horses were administered 300 mg of PB by IV-RLP in 1 randomly selected pelvic limb in a manner identical to that used in experiment 1.

RESULTS

For all 3 doses, the mean synovial fluid PB concentration was > 10 times the therapeutic concentration and below the level of quantification at 30 and 1,440 minutes after drug administration, respectively. No adverse systemic or local effects were observed following PB administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that IV-RLP of PB might be a viable alternative for treatment of horses with synovial infections caused by gram-negative bacteria.

Abstract

OBJECTIVE

To determine whether therapeutic concentrations (> 0.5 to 1.0 μg/mL) of polymyxin B (PB) were achieved in the tarsocrural joint of horses when the drug was administered by IV regional limb perfusion (IV-RLP) via a saphenous vein at doses of 25, 50, and 300 mg and to describe any adverse systemic or local effects associated with such administration.

ANIMALS

9 healthy adult horses.

PROCEDURES

In the first of 2 experiments, 6 horses each received 25 and 50 mg of PB by IV-RLP via a saphenous vein with at least 2 weeks between treatments. For each treatment, a tourniquet was placed at the midmetatarsus and another was placed midway between the stifle joint and tarsus. Both tourniquets were removed 30 minutes after the assigned dose was administered. Blood and tarsocrural joint fluid samples were collected for determination of PB concentration before and at predetermined times after drug administration. In experiment 2, 4 horses were administered 300 mg of PB by IV-RLP in 1 randomly selected pelvic limb in a manner identical to that used in experiment 1.

RESULTS

For all 3 doses, the mean synovial fluid PB concentration was > 10 times the therapeutic concentration and below the level of quantification at 30 and 1,440 minutes after drug administration, respectively. No adverse systemic or local effects were observed following PB administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that IV-RLP of PB might be a viable alternative for treatment of horses with synovial infections caused by gram-negative bacteria.

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