Pharmacokinetics of oral firocoxib in un-weaned calves.

The objective of this study was to determine the pharmacokinetics of firocoxib after oral administration in un-weaned calves. Eight Holstein calves with a mean age of 36 days and a mean weight of 55 kg were administered a single oral dose of 227 mg firocoxib. The resulting mean dosage was 4.2 mg/kg (range 3.5-5.0 mg/kg). Blood was collected prior to drug administration and at 2, 4, 6, 8, 24, 48, 72, and 96 h after treatment. Firocoxib concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Using computer software, pharmacokinetic parameters were found to fit best with a one-compartment model. Mean Cmax was 0.9 µg/ml (range 0.570-1.254), and Tmax was estimated to be 7 h (range 4-8 h). The estimated T1/2 was 15.3 h. The pharmacokinetics of firocoxib after oral dosing are similar to those in dogs, with the exception of a T1/2 that is approximately twice as long. Based on the similar pharmacokinetics, it is possible that a dose of 227 mg firocoxib orally could provide an analgesic effect in un-weaned calves.

Plasma disposition of ceftazidime in healthy neonatal foals following intravenous and intramuscular administration.

Cephalosporin antimicrobials can be utilized for the treatment of sepsis in neonatal foals, particularly when an aminoglycoside is contraindicated. Some cephalosporins, however, are not utilized because of cost, sporadic availability, or uncertainty about efficacy. The plasma disposition of ceftazidime, a third-generation cephalosporin with a broad spectrum of activity against a wide variety of gram-negative bacteria and minimal renal side effects has not been reported in neonatal foals. In this study, the plasma disposition of single intravenous (IV) and intramuscular (IM) doses of ceftazidime in neonatal foals was determined. Six healthy one to two-day-old foals were given 25 mg/kg of ceftazidime by IV and IM routes in a cross-over design, with a 48-h washout period between doses. Non-compartmental analysis was used to estimate plasma pharmacokinetic parameters. Median t1/2 was 2 h and median AUC0-last was 364 µg h/ml for both IV and IM administration. Median Cmax after IM administration was 101 µg/ml, with a median Tmax of 0.7 h. Relative bioavailability of IM injection was 90%. There were no statistically significant differences between estimated IV and IM pharmacokinetic parameters. Plasma concentrations remained above the human CLSI susceptible breakpoint for Enterobacteriaceae for over 8 h following IV and IM administration.

Pharmacokinetics of tulathromycin in fetal sheep and pregnant ewes.

Macrolides are important antimicrobials frequently used in human and veterinary medicine in the treatment of pregnant women and pregnant livestock. They may be useful for the control of infectious ovine abortion, which has economic, animal health, and human health impacts. In this study, catheters were surgically placed in the fetal vasculature and amnion of pregnant ewes at 115 (±2) days of gestation. Ewes were given a single dose of 2.5 mg/kg tulathromycin subcutaneously, and drug concentrations were determined in fetal plasma, maternal plasma, and amniotic fluid at 4, 8, 12, 24, 36, 48, 72, 144, and 288 hr after drug administration. Pharmacokinetic parameters in maternal plasma were estimated using noncompartmental analysis and were similar to those previously reported in nonpregnant ewes. Tulathromycin was present in fetal plasma and amniotic fluid, indicating therapeutic potential for use against organisms in these compartments, though concentrations were lower than those in maternal plasma. Time-course of drug concentrations in the fetus was quite different than that in the ewe, with plasma concentrations reaching a plateau at 4 hr and remaining at this concentration for the remainder of the sampling period (288 hr), raising questions about how tulathromycin may be transported into or metabolized and eliminated by the fetus.

Pharmacokinetics of ceftiofur crystalline-free acid in plasma and seminal plasma in beef bulls.

The objective of this study was to compare the plasma (PL) and seminal plasma (SP) pharmacokinetic profile of ceftiofur (CEFT) and desuroylceftiofur acetamide (DFCA) after administration of CEFT crystalline-free acid (CCFA) by SC route in two sites of the ear in beef bulls. Four clinically healthy Hereford bulls received a comprehensive physical exam and subsequently a breeding-soundness examination, CBC, and chemistry profile panel. All bulls were diagnosed healthy and satisfactory potential breeders. In one group (n = 2), a single dose of CCFA was administered SC route at the base of the ear (BOE) at a dose of 6.6 mg/kg of body weight. The second group (n = 2) was also administered by SC route in the middle third of the posterior aspect of the ear (MTE). The concentrations of CEFT and DFCA in PL and SP were determined by a high-performance liquid chromatography mass spectrometry (HPLC-MS). Blood and semen samples were collected before the administration of CCFA and at 12, 24, 36, 48, 72, 96, 120, 144, and 168 h after injection. No levels of CEFT were detected in PL and only in 20 of the 40 SP samples (P = 0.0001). The mean level of CEFT in SP was 0.11 % in comparison with the DFCA level. DFCA was found in all PL and SP samples. Therefore, DFCA was chosen to be utilized in the study of the pharmacokinetics parameters both in PL and SP. There were no differences in the mean PL levels of DFCA for the two sites of SC administration between the BOE (102.9 ± 78.9 ng/mL; X ± SD) and to MTE (116.1 ± 70.2 ng/mL; P = 0.58). The mean SP levels of DFCA after administration in the BOE was 857 ± 747 ng/mL, and for the MTE was 549 ± 488 ng/mL without differences between both sites (P = 0.15). The mean level of DFCA in PL was 109.5 ± 74.0 ng/mL, which was lower than the mean SP levels of 695 ± 103 ng/mL (P = 0.001). Moreover, the PL peak DFCA concentration (Cmax) was 229 ± 46 ng/mL at 36.0 ± 29.4 h (Tmax) post-administration. The SP Cmax was 1851 ± 533 ng/mL at 30.0 ± 28.6 h (Tmax) post-administration. The Cmax between PL and SP were distinctive (P = 0.004) without any differences in Tmax between PL and SP (P = 0.60). The terminal half-life for PL DFCA (47.4 ± 29.3 h) was not different than in SP (53.1 ± 23.6 h; P = 0.77). The PL area under the curve concentration time from the first to the last sample (AUC0-last) was 18,984 ± 4841 ng/mL/h, which was significatively smaller compared with 125,677 ± 59,445 ng/mL/h for SP AUC0-last (P = 0.04). The PL mean residence time from the first to the last sample (MRT0-last) was 69.7 ± 15.1 h, and it was similar than for SP of 66.5 ± 7.7 h (P = 0.69). From the present investigation, based in its pharmacokinetic features, it was concluded that CCFA should be an appropriate antibiotic that could be used for the treatment of bull genital infections when its indication is properly outlined. To study the pharmacokinetics of CCFA in SP, DFCA metabolite was appropriated.

Evaluation of an Oral Supplemental Cannabidiol Product for Acceptability and Performance in Mature Horses.

Thirty stock type geldings (15 ± 3 years; 556 ± 63 kg BW) were used in a randomized complete design over 28 days to determine the influence of cannabidiol (CBD) oil supplementation levels on body weight, body condition, and blood chemistry. Horses were randomly assigned to one of three dietary treatments (n = 10 per treatment) formulated with canola oil to provide 1.50 mg CBD/kg BW (TRTA), 0.75 mg CBD/kg BW (TRTB), or 0.00 mg CBD/kg BW (canola oil; CTRL). Treatments were top-dressed onto concentrate and individually administered twice daily. Horses were maintained in adjacent dry lots and received coastal bermudagrass hay ad libitum. Body weight and body condition scores (BCS) were obtained every 14 days. On day 0 and 28, blood was collected via jugular venipuncture and serum was harvested to perform a blood chemistry panel and drugs of abuse screening at the Texas Veterinary Medical Diagnostic Laboratory. Data were analyzed using PROC MIXED of SAS (v9.4), and the model included treatment, time, and the treatment × time interaction, and linear and quadratic orthogonal polynomial contrasts to partition sum of squares. Analysis of composited treatment samples revealed lower CBD concentrations than indicated from initial testing by the manufacturer (0.13 mg CBD/kg in TRTA; 0.12 mg CBD/kg in TRTB). At this level of supplementation, canola-based CBD oil was well-accepted by mature horses, banned substances were not detectable in blood, and blood chemistry parameters were not adversely affected as a result of supplementation. More research is warranted to describe the discrepancy between formulated levels compared to tested levels of CBD in the canola-based supplement.

Lack of Absorption of a Sustained-release Buprenorphine Formulation Administered Subcutaneously to Athymic Nude Rats.

Female athymic nude rats (Rattus norvegicus; n = 45; age, 6 wk) were used in an IACUC-approved protocol to investigate mechanisms and potential treatments associated with brain, spine, and spinal cord metastases from triple negative breast cancer. The analgesic plan included the use of buprenorphine SR LAB (0.6 mg/kg; 0.11 mL/rat) subcutaneously and an oral NSAID delivered via the water. Thirty-seven rats reached the experimental end point at 3 mo after xenotransplantation and were euthanized for tissue harvest. Grossly, all 37 rats had nodules in the subcutis over the shoulders; these were identified as small, cystic structures (diameter, approximately 0.25 cm). The cysts and haired skin were submitted for LC-MS/MS (liquid chromatography-tandem mass spectrometry) and histopathology. Histologically, the cysts were lined by fibrous connective tissue mildly infiltrated by macrophages, lymphocytes, and plasma cells. Adjacent blood vessels were rimmed by a mild infiltrate of lymphocytes and plasma cells. The cysts contained variable accumulations of a light pink, proteinaceous fluid. The cause for the cysts could not be determined histologically; there was no evidence of neoplasia. LC-MS/MS analysis revealed that the cysts contained buprenorphine. We hypothesize that the lack of T cells and a cell-mediated immune response in these rats prevented the dissolution of the vehicle and absorption of the buprenorphine. The manufacturer provides a cautionary statement regarding the use of this formulation in nude mice due to skin reactions, but to our knowledge, this report is the first description of an apparent lack of absorption of the drug in immunodeficient animals.

Oxytetracycline concentrations in interstitial fluid from tissue chambers inoculated with Corynebacterium pseudotuberculosis after intramuscular or intrachamber administration in sheep.

OBJECTIVE: To determine oxytetracycline concentrations in plasma and in fluid from Corynebacterium pseudotuberculosis (CPT)-inoculated tissue chambers (used as experimental abscess models) and uninoculated (control) tissue chambers in sheep after IM or local administration of the drug and to investigate whether CPT growth was reduced or eliminated by these treatments. ANIMALS: 10 clinically normal female sheep. PROCEDURES: Sterile tissue chambers were surgically implanted in both paralumbar fossae of each sheep; ≥ 2 weeks later (day -6), 1 randomly selected chamber was inoculated with CPT, and the opposite chamber was injected with sterile growth medium. Sheep received oxytetracycline IM (n = 5) or by percutaneous injection into CPT-inoculated (4) or uninoculated (1) chambers on day 0. Tissue fluid from each chamber and venous blood samples for plasma collection were obtained at predetermined times over 6 days for bacterial counts (tissue chambers) and analysis of oxytetracycline concentrations (tissue chambers and plasma). Sheep were euthanized on day 6. Regional lymph nodes were collected bilaterally from each sheep for culture. RESULTS: Measurable concentrations of oxytetracycline were present in each chamber throughout the study, regardless of administration route or presence of CPT. No CPT growth was detected after the 48-hour time point in inoculated chambers injected with oxytetracycline; however, CPT was isolated from all inoculated chambers throughout the study after IM drug administration. One regional lymph node (ipsilateral to a CPT-inoculated, oxytetracycline-injected chamber with no CPT growth after 48 hours) was culture positive for CPT. CONCLUSIONS AND CLINICAL RELEVANCE: Intralesional administration of oxytetracycline may eliminate growth of CPT locally, but complete elimination of the organism remains difficult.

SiO2-RuO2: a stable electrocatalyst support.

High surface area SiO2-RuO2 (SRO) supports with various SiO2: RuO2 ratios were synthesized using a wet chemical method. The supports were catalyzed by depositing platinum nanoparticles on their surface. The synthesized materials were characterized by XRD, TEM, BET, and linear sweep voltammetry to study microstructure and properties. The electrochemical stability, electrochemical surface area, electrocatalytic activity and fuel cell performance were also measured. The optimal 1:1 mol ratio of SiO2-RuO2 (SRO-1) possessed a BET surface area of 305 m²/g and an electrical conductivity of 24 S/cm. This SRO support demonstrated 10-fold higher electrochemical stability than Vulcan XC-72R carbon when subjected to an aggressive accelerated stability test (AST) involving 10,000 potential cycles between 1 and 1.5 V. The mass activity of Pt-doped SRO-1 was 54 mA/mg(Pt), whereas its specific activity was 115 µA cm(Pt)⁻². The fuel cell performance obtained with this catalyst was lower, but compared favorably against a commercial Pt/C baseline. Analysis of fuel cell performance data confirmed that the lower fuel cell performance resulted largely from ohmic and mass transport losses within the unoptimized electrocatalyst layer.