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Abstract

Objective—To compare isolated limb retrograde venous injection (ILRVI) and isolated limb infusion (ILI) for delivery of amikacin to the synovial fluid of the distal interphalangeal and metacarpophalangeal joints and to evaluate the efficacy of use of an Esmarch tourniquet in standing horses.

Animals—6 healthy adult horses.

Procedures—Horses were randomly assigned in a crossover design. In ILRVI, the injection consisted of 1 g of amikacin diluted to a total volume of 60 mL administered during a 3-minute period. In ILI, the infusion consisted of 1 g of amikacin diluted to 40 mL administered during a 3-minute period followed by administration of boluses of diluent (82 mL total) to maintain vascular pressure. During ILI, the infusate and blood were circulated from the venous to the arterial circulation in 5-mL aliquots. Synovial fluid and serum samples were obtained to determine maximum amikacin concentrations and tourniquet leakage, respectively.

Results—Both techniques yielded synovial concentrations of amikacin > 10 times the minimum inhibitory concentration (MIC) for 90% of isolates (80 μg/mL) and > 10 times the MIC breakpoint (160 μg/mL) of amikacin-susceptible bacteria reported to cause septic arthritis in horses. These values were attained for both joints for both techniques. Esmarch tourniquets prevented detectable loss of amikacin to the systemic circulation for both techniques.

Conclusions and Clinical Relevance—Both techniques reliably achieved synovial fluid concentrations of amikacin consistent with concentration-dependent killing for bacteria commonly encountered in horses with septic arthritis. Esmarch tourniquets were effective for both delivery techniques in standing horses.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses.

Animals—11 healthy adult horses.

Procedure—Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured.

Results—Mean ± SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 ± 0.37 μg/mL, 2.35 ± 0.78 μg/mL, and 2.40 ± 0.29 μg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean ± SD voriconazole concentration in AH after a single orally administered dose was 0.86 ± 0.22 μg/mL.

Conclusions and Clinical Relevance—Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots.

Animals—20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh).

Procedures—In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments).

Results—Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group.

Conclusions and Clinical Relevance—In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole ≤ 0.4 μg/mL. Higher doses may be needed to maintain plasma voriconazole concentrations during long-term treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum.

Animals—18 horses.

Procedures—Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed.

Results—Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flu-nixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cy-clooxygenase-independent effects.

Conclusions and Clinical Relevance—Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the outcome of and prognostic indicators for dogs and cats with pneumoperitoneum and no history of penetrating trauma.

Design—Retrospective study.

Animals—43 dogs and 11 cats.

Procedure—Medical records of dogs and cats with radiographic evidence of pneumoperitoneum and no history of penetrating trauma were reviewed. Information collected included signalment, previous medical problems, initial complaint, duration of illness, physical examination findings, radiographic findings, laboratory abnormalities, abdominocentesis results, bacterial culture results, concurrent diseases, hospitalization time, and outcome. Abdominal radiographs were reviewed, and radiographic severity of pneumoperitoneum was classified. For those animals that underwent exploratory laparotomy, time from admission to surgery and results of histologic examination of biopsy specimens were recorded.

Results—24 (44%) animals survived and were discharged from the hospital, but none of the variables examined was associated with whether animals survived. Rupture of the gastrointestinal tract was the cause of pneumoperitoneum in 40 animals. However, cause and location of gastrointestinal tract rupture was not associated with whether animals survived. Twenty-three of 40 (58%) animals that underwent exploratory laparotomy survived, compared with only 1 of 14 animals that did not undergo surgery.

Conclusions and Clinical Relevance—Results suggest that pneumoperitoneum in dogs and cats without any history of penetrating trauma is most commonly associated with rupture of the gastrointestinal tract and requires immediate surgical intervention. Even when appropriate treatment is instituted, the shortterm prognosis is only fair. (J Am Vet Med Assoc 2004;225:251–255)

Full access
in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE

To compare the elution characteristics of amikacin-impregnated calcium sulfate (CaSO4) beads based on different drug concentrations and bead size configurations.

SAMPLE

Six groups of amikacin-impregnated CaSO4 beads and one negative control group.

PROCEDURES

Amikacin-impregnated CaSO4 beads were formed with either 500 mg (low-concentration) or 1 g (high-concentration) of amikacin per 15 g CaSO4 hemihydrate powder. The number of beads necessary to approximate 150 mg of amikacin for each of the 3 bead sizes (3 mm, 5 mm, and 7 mm) at both low and high concentrations were placed in 6 mL of phosphate-buffered saline. The saline was sampled at 14 time points over 28 days. Amikacin concentrations were determined using liquid chromatography-mass spectrometry.

RESULTS

Smaller beads reached higher mean peak concentrations than larger beads (P < .0006). Peak concentrations for the low- and high-concentration groups were 20.5 mg/mL and 27.4 mg/mL, 13.1 mg/mL and 14.0 mg/mL, and 8.85 mg/mL and 6.75 mg/mL for the 3 mm, 5 mm, and 7 mm beads, respectively. Bead size also affected the length of therapeutic duration, lasting 6 days for the 3 mm and 5 mm beads and 9 days for the 7 mm beads. However, this was only statistically evident among the high-concentration beads (P < .044). Antimicrobial concentration within the same bead sizes did not affect elution.

CLINICAL RELEVANCE

Amikacin-impregnated CaSO4 beads achieved extreme supratherapeutic eluent concentrations. While additional studies are needed, bead size significantly affected elution with smaller beads reaching higher peak concentrations and 7 mm, high-concentration beads demonstrating a longer therapeutic duration than smaller beads.

Open access
in American Journal of Veterinary Research

Abstract

Objective—To determine the degree of ocular penetration and systemic absorption of commercially available topical ophthalmic solutions of 0.3% ciprofloxacin and 0.5% moxifloxacin following repeated topical ocular administration in ophthalmologically normal horses.

Animals—7 healthy adult horses with clinically normal eyes as evaluated prior to each treatment.

Procedures—6 horses were used for assessment of each antimicrobial, and 1 eye of each horse was treated with topically administered 0.3% ciprofloxacin or 0.5% moxifloxacin (n = 6 eyes/drug) every 4 hours for 7 doses. Anterior chamber paracentesis was performed 1 hour after the final dose was administered, and blood samples were collected at 24 (immediately after the final dose), 24.25, 24.5, and 25 hours (time of aqueous humor [AH] collection). Plasma and AH concentrations of ciprofloxacin or moxifloxacin were determined by use of high-performance liquid chromatography.

Results—Mean ± SD AH concentrations of ciprofloxacin and moxifloxacin were 0.009 ± 0.008 μg/mL and 0.071 ± 0.029 μg/mL, respectively. The AH moxifloxacin concentrations were significantly greater than those of ciprofloxacin. Mean ± SD plasma concentrations of ciprofloxacin were less than the lower limit of quantification. Moxifloxacin was detected in the plasma of all horses at all sample collection times, with a peak value of 0.015 μg/mL at 24 and 24.25 hours, decreasing to < 0.004 μg/mL at 25 hours.

Conclusions and Clinical Relevance—Moxifloxacin was better able to penetrate healthy equine corneas and reach measurable AH concentrations than was ciprofloxacin, suggesting moxifloxacin might be of greater value in the treatment of deep corneal or intraocular bacterial infections caused by susceptible organisms. Topical administration of moxifloxacin also resulted in detectable plasma concentrations.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine elimination kinetics of tilmicosin in milk following intramammary administration in lactating dairy cattle.

Design—Prospective pharmacokinetic study.

Animals—6 lactating dairy cows.

Procedures—Following collection of baseline milk samples, 1,200 mg (4 mL) of tilmicosin was infused into the left front and right rear mammary glands of each cow. Approximately 12 hours later, an additional 1,200 mg of tilmicosin was infused into the left front and right rear glands after milking. Milk samples were then collected from each gland at milking time for 40 days. Concentration of tilmicosin was determined by means of ultraperformance liquid chromatography–mass spectrometry, and a milk withdrawal interval for tilmicosin was calculated on the basis of the tolerance limit method.

Results—Although there was considerable variation between glands, concentration of tilmicosin was high in milk from treated glands and had a long half-life in treated and untreated glands. Tilmicosin was detected in all treated glands for the entire 40-day study period and was detected in untreated glands for approximately 30 to 35 days.

Conclusions and Clinical Relevance—Findings indicated that tilmicosin should not be administered by the intramammary route in lactating dairy cows. Milk from all glands of any cows accidentally treated should be discarded for a minimum of 82 days following intramammary administration.

Full access
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association