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1.  Synovial fluid pharmacokinetics of tulathromycin, gamithromycin and florfenicol after a single subcutaneous dose in cattle 
Deep digital septic conditions represent some of the most refractory causes of severe lameness in cattle. The objective of this study was to determine the distribution of tulathromycin, gamithromycin and florfenicol into the synovial fluid of the metatarsophalangeal (MTP) joint of cattle after single subcutaneous administration of drug to evaluate the potential usefulness of these single-dose, long-acting antimicrobials for treating bacterial infections of the joints in cattle.
Twelve cross-bred beef cows were randomly assigned to one of the drugs. Following subcutaneous administration, arthrocentesis of the left metatarsophalangeal joint was performed at various time points up to 240 hours post-injection, and samples were analyzed for drug concentration. In synovial fluid, florfenicol pharmacokinetic parameters estimates were: mean Tmax 7 +/− 2 hours, mean t½ 64.9 +/− 20.1 hours and mean AUC0-inf 154.0 +/− 26.2 ug*h/mL. Gamithromycin synovial fluid pharmacokinetic parameters estimates were: mean Tmax 8 hours, mean t½ 77.9 +/− 30.0 hours, and AUC0-inf 6.5 +/− 2.9 ug*h/mL. Tulathromycin pharmacokinetic parameters estimates in synovial fluid were: Tmax 19 +/− 10 hours, t½ 109 +/− 53.9 hours, and AUC0-inf 57.6 +/− 28.2 ug h/mL.
In conclusion, synovial fluid concentrations of all three antimicrobials were higher for a longer duration than that of previously reported plasma values. Although clinical data are needed to confirm microbiological efficacy, florfenicol achieved a synovial fluid concentration greater than the MIC90 for F. necrophorum for at least 6 days.
PMCID: PMC4332912
Synovial fluid; Tulathromycin; Gamithromycin; Florfenicol; Pharmacokinetics; Bovine
2.  Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration 
The purpose of this study was to determine intravenous (IV), intramuscular (IM) and oral (PO) FM PK in mature swine. Appropriate pain management for lameness in swine is a critical control point for veterinarians and producers, but science-based guidance on optimal housing, management and treatment of lameness is deficient. Six mature swine (121–168 kg) were administered an IV, IM, or PO dose of flunixin meglumine at a target dose of 2.2 mg/kg in a cross-over design with a 10 day washout period between treatments. Plasma samples collected up to 48 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by non-compartmental pharmacokinetic analysis.
No adverse effects were observed with flunixin meglumine administration for all routes. Flunixin meglumine was administered at an actual mean dose of 2.21 mg/kg (range: 2.05-2.48 mg/kg) IV, IM and PO. A mean peak plasma concentration (CMAX) for IM and PO administration was 3748 ng/ml (range: 2749–6004 ng/ml) and 946 ng/ml (range: 554–1593 ng/ml), respectively. TMAX was recorded at 1.00 hour (range: 0.50-2.00 hours) and 0.61 hours (range: 0.17-2.00 hours) after PO and IM administration. Half-life (T ½ λz) for IV, IM and PO administration was 6.29 hours (range: 4.84-8.34 hours), 7.49 hours (range: 5.55-12.98 hours) and 7.08 hours (range: 5.29-9.15 hours) respectively. In comparison, bioavailability (F) for PO administration was 22% (range: 11-44%) compared to IM F at 76% (range: 54-92%).
The results of the present study suggest that FM oral administration is not the most effective administration route for mature swine when compared to IV and IM. Lower F and Cmax of PO-FM in comparison to IM-FM suggest that PO-FM is less likely to be an effective therapeutic administration route.
PMCID: PMC3751365  PMID: 23941181
Swine; Gilt; Lameness; Flunixin meglumine; Pharmacokinetics; NSAIDs; Oral bioavailability
3.  Pharmacokinetics and effect of intravenous meloxicam in weaned Holstein calves following scoop dehorning without local anesthesia 
Dehorning is a common practice involving calves on dairy operations in the United States. However, less than 20% of producers report using analgesics or anesthetics during dehorning. Administration of a systemic analgesic drug at the time of dehorning may be attractive to dairy producers since cornual nerve blocks require 10 – 15 min to take effect and only provide pain relief for a few hours. The primary objectives of this trial were to (1) describe the compartmental pharmacokinetics of meloxicam in calves after IV administration at 0.5 mg/kg and (2) to determine the effect of meloxicam (n = 6) or placebo (n = 6) treatment on serum cortisol response, plasma substance P (SP) concentrations, heart rate (HR), activity and weight gain in calves after scoop dehorning and thermocautery without local anesthesia.
Plasma meloxicam concentrations were detectable for 50 h post-administration and fit a 2-compartment model with a rapid distribution phase (mean T½α = 0.22 ± 0.087 h) and a slower elimination phase (mean T½β = 21.86 ± 3.03 h). Dehorning caused a significant increase in serum cortisol concentrations and HR (P < 0.05). HR was significantly lower in the meloxicam-treated calves compared with placebo-treated calves at 8 h (P = 0.039) and 10 h (P = 0.044) after dehorning. Mean plasma SP concentrations were lower in meloxicam treated calves (71.36 ± 20.84 pg/mL) compared with control calves (114.70 ± 20.84 pg/mL) (P = 0.038). Furthermore, the change in plasma SP from baseline was inversely proportional to corresponding plasma meloxicam concentrations (P = 0.008). The effect of dehorning on lying behavior was less significant in meloxicam-treated calves (p = 0.40) compared to the placebo-treated calves (P < 0.01). Calves receiving meloxicam prior to dehorning gained on average 1.05 ± 0.13 kg bodyweight/day over 10 days post-dehorning compared with 0.40 ± 0.25 kg bodyweight/day in the placebo-treated calves (p = 0.042).
To our knowledge, this is the first published report examining the effects of meloxicam without local anesthesia on SP, activity and performance of calves post-dehorning. These findings suggest that administration of meloxicam alone immediately prior to dehorning does not mitigate signs of acute distress but may have long term physiological, behavior and performance effects.
PMCID: PMC3503738  PMID: 22937949
Analgesia; Meloxicam; Dehorning; Substance P; Cortisol; Heart rate; Accelerometers; Performance
4.  Bioavailability and pharmacokinetics of oral meloxicam in llamas 
South American camelids in the United States have rapidly developed into an important agricultural industry in need of veterinary services. Pain management is challenging in camelids because there are no drugs currently approved by the U.S. Food and Drug Administration for use in these species. Dosage regimens used for many therapeutic drugs have been extrapolated from other ruminants; however, the pharmacokinetics, in camelids, may differ from those of other species. Studies investigating the pharmacokinetics of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs in camelids are deficient in the published literature. Six adult llamas (121- 168 kg) were administered either a 1 mg/kg dose of oral or a 0.5 mg/kg dose of IV meloxicam in a randomized cross-over design with an 11 day washout period between treatments. Plasma samples collected up to 96 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry detection (HPLC-MS) followed by non-compartmental pharmacokinetic analysis.
A mean peak plasma concentration (CMAX) of 1.314 μg/mL (Range: 0.826 – 1.776 μg/mL) was recorded at 21.4 hours (Range: 12.0 – 24.0 hours) with a half-life (T ½ λz) of 22.7 hours (Range: 18.0 – 30.8 hours) after oral meloxicam administration. In comparison, a half-life (T ½ λz) of 17.4 hours (Range: 16.2 – 20.7 hours) was demonstrated with IV meloxicam administration. The oral bioavailability (F) of meloxicam (dose normalized) was 76% (Range: 48 – 92%). No adverse effects associated with either treatment modality were observed in the llamas.
The mean bioavailability (F) of oral meloxicam was 76% indicating a high degree of gastrointestinal absorption. Plasma meloxicam concentrations >0.2 μg/mL were maintained for up to 72 h after oral administration; >0.2 μg/mL is considered to be the concentration of meloxicam required for analgesic effects in other species such as the horse. These data suggest that a single dosage of oral meloxicam at 1 mg/kg could potentially maintain therapeutic concentrations in plasma for up to 3 days in adult llamas.
PMCID: PMC3476427  PMID: 22720782
Camelid; Llama; Pharmacokinetics; Meloxicam; NSAIDS; Oral bioavailability
5.  Assessment of behavioral changes associated with oral meloxicam administration at time of dehorning in calves using a remote triangulation device and accelerometers 
Dehorning is common in the cattle industry, and there is a need for research evaluating pain mitigation techniques. The objective of this study was to determine the effects of oral meloxicam, a non-steroidal anti-inflammatory, on cattle behavior post-dehorning by monitoring the percent of time spent standing, walking, and lying in specific locations within the pen using accelerometers and a remote triangulation device. Twelve calves approximately ten weeks of age were randomized into 2 treatment groups (meloxicam or control) in a complete block design by body weight. Six calves were orally administered 0.5 mg/kg meloxicam at the time of dehorning and six calves served as negative controls. All calves were dehorned using thermocautery and behavior of each calf was continuously monitored for 7 days after dehorning using accelerometers and a remote triangulation device. Accelerometers monitored lying behavior and the remote triangulation device was used to monitor each calf’s movement within the pen.
Analysis of behavioral data revealed significant interactions between treatment (meloxicam vs. control) and the number of days post dehorning. Calves that received meloxicam spent more time at the grain bunk on trial days 2 and 6 post-dehorning; spent more time lying down on days 1, 2, 3, and 4; and less time at the hay feeder on days 0 and 1 compared to the control group. Meloxicam calves tended to walk more at the beginning and end of the trial compared to the control group. By day 5, the meloxicam and control group exhibited similar behaviors.
The noted behavioral changes provide evidence of differences associated with meloxicam administration. More studies need to be performed to evaluate the relationship of behavior monitoring and post-operative pain. To our knowledge this is the first published report demonstrating behavioral changes following dehorning using a remote triangulation device in conjunction with accelerometers.
PMCID: PMC3485124  PMID: 22546492
Oral meloxicam; Behavior; Dehorn; Remote triangulation device
6.  A survey of castration methods and associated livestock management practices performed by bovine veterinarians in the United States 
Castration of male calves destined for beef production is a common management practice performed in the United States amounting to approximately 15 million procedures per year. Societal concern about the moral and ethical treatment of animals is increasing. Therefore, production agriculture is faced with the challenge of formulating animal welfare policies relating to routine management practices such as castration. To enable the livestock industry to effectively respond to these challenges there is a need for more data on management practices that are commonly used in cattle production systems. The objective of this survey was to describe castration methods, adverse events and husbandry procedures performed by U.S. veterinarians at the time of castration. Invitations to participate in the survey were sent to email addresses of 1,669 members of the American Association of Bovine Practitioners and 303 members of the Academy of Veterinary Consultants.
After partially completed surveys and missing data were omitted, 189 responses were included in the analysis. Surgical castration with a scalpel followed by testicular removal by twisting (calves <90 kg) or an emasculator (calves >90 kg) was the most common method of castration used. The potential risk of injury to the operator, size of the calf, handling facilities and experience with the technique were the most important considerations used to determine the method of castration used. Swelling, stiffness and increased lying time were the most prevalent adverse events observed following castration. One in five practitioners report using an analgesic or local anesthetic at the time of castration. Approximately 90% of respondents indicated that they vaccinate and dehorn calves at the time of castration. Over half the respondents use disinfectants, prophylactic antimicrobials and tetanus toxoid to reduce complications following castration.
The results of this survey describe current methods of castration and associated management practices employed by bovine veterinarians in the U.S. Such data are needed to guide future animal well-being research, the outcomes of which can be used to develop industry-relevant welfare guidelines.
PMCID: PMC2841153  PMID: 20199669

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