Journal of veterinary pharmacology and therapeutics最新文献

Despite their widespread clinical use, there is limited pharmacokinetic data for many equine intrauterine antimicrobials. This study aimed to measure the concentration of gentamicin and penicillin in the uterine fluid of mares following infusion of either a standard (PPGent) or long-acting (LA-PPGent) compounded formulation. We hypothesized that both formulations would result in therapeutic concentrations, with total concentrations sustained for longer using the long-acting formulation. Mares were administered 2400 mg of procaine penicillin and 200 mg of gentamicin via a single intrauterine infusion in either a standard (n = 6) or a lyophilized formulation suspended in a slow-release matrix (n = 6). Intrauterine fluid was collected over a 72-h period and analyzed for antibiotic concentrations using high-performance liquid chromatography and ultra-high-performance liquid chromatography and tandem mass spectrometry. Mean maximal concentrations were seen at 0.5 h in group PPGent (Penicillin: 10,123.0 ± 4298.0 μg/mL, Gentamicin: 3397.3 ± 1338.5 μg/mL) and exceeded MIC for relevant organisms for 72 h (Penicillin: 2.59 ± 6.34 μg/mL, Gentamicin: 2.14 ± 2.4 μg/mL). Interestingly, maximal concentrations were lower in group LA-PPG (Penicillin: 2213.8 ± 967.8 μg/mL—p < 0.05, Gentamicin: 1859 ± 2413 μg/mL) and exceeded MIC for a shorter period of time than the unmodified mixture of commonly used FDA-approved antibiotics.

Building the skills and knowledge necessary to practice evidence-based veterinary medicine (EBVM) should occur throughout the veterinary curriculum. Operationalizing EBVM includes asking a clinical question in PICO format, searching the biomedical literature for evidence, critically appraising the evidence, and applying the evidence to make a clinical recommendation. At the Texas A&M University College of Veterinary Medicine & Biomedical Sciences, we have embedded EBVM skill-reinforcing assignments into two clinical rotations, Dermatology and Food Animal Medicine and Surgery. In this paper, we describe the implementation and the evolution of assignments, including the learning objectives, workflow, and grading rubrics. We also summarize the types of PICO questions pursued by students. We conclude with the pharmacologist's and the clinicians' reflections on the value of the assignments and the approach of collaboration among specialists.

Levetiracetam (LEV) is a commonly used antiseizure medication in dogs, available in immediate-release (LEV-IR) and extended-release (LEV-XR) formulations. LEV-XR improves owner compliance with less frequent dosing, but its lowest concentration tablet (500 mg) often exceeds recommended doses for small dogs. This study evaluated how modifying LEV-XR tablets affects dissolution rates, comparing intact, split, and crushed LEV-XR tablets with intact LEV-IR tablets. Dissolution testing followed United States Pharmacopeia (USP) guidelines for LEV-XR tablets. Tablets were placed in a buffer solution (pH 6.0) and agitated at 100 rpm. Samples were collected at 0, 0.5, 2, 4, 6, and 8 h, then analyzed by high-pressure liquid chromatography (HPLC) using a USP reference standard. Results indicated that splitting LEV-XR tablets slightly increased drug release compared to intact tablets, while crushing eliminated extended-release properties, mimicking LEV-IR dissolution. These findings suggest that splitting LEV-XR tablets may be a viable strategy for dosing small dogs without compromising sustained release. Conversely, crushing LEV-XR tablets may be useful for rapid drug release in cluster seizure protocols. Future pharmacokinetic studies are needed to confirm if these in vitro results correlate with in vivo performance for both maintenance and emergency seizure management in dogs.

A randomized, blinded, placebo-controlled crossover study was performed with eight professional working dogs to evaluate the pharmacokinetics and pharmacodynamics of three opioid reversal agents. Following sedation with 1 mg kg⁻¹ methadone HCl IV, dogs were randomly assigned to receive naloxone, naltrexone, or nalmefene at 0.1 mg kg⁻¹ IM, or saline (0.1 mL kg⁻¹). Sedation scores and vital signs were obtained for 6 h, and blood samples were obtained for 72 h. Across all groups and phases, the mean sedation score prior to methadone was 0.93/14, and prior to reversal/placebo was 11.45/14. Mean sedation scores 1 min post reversal/placebo were 7.6, 7.4, 8.1, and 10.6; and at 5 min were 2.2, 1.9, 1.9, and 11.8 for nalmefene, naloxone, naltrexone, and saline, respectively. Dogs with a sedation score ≥ 10/14 at 20 min after reversal/placebo were administered 0.1 mg kg⁻¹ of naloxone IM and included all dogs that received saline. The reversal agents significantly decreased sedation scores within 5 min (p < 0.001) and reversal was maintained for the duration of the study. A previously undetected slower terminal elimination phase was observed for all analytes between 24 and 72 h; however, future studies with additional time points between 6 and 24 h are needed to generate pharmacokinetic estimates for this phase. These reversal agents may be useful for treating sedation in professional working dogs exposed to opioids prior to seeking veterinary care. Pharmacological differences between methadone and higher potency opioids (fentanyl and its derivatives) preclude interpretation of these findings to non-methadone opioids, and further studies are needed.

Veterinary Nurses play a key role in handling drugs and perform medication treatments, thus pharmacological knowledge is essential. The veterinary nurses' role varies widely worldwide but does not include the prescription of drugs. Nevertheless, pharmacology is a complex subject within veterinary nursing education and for the registered veterinary nurse in practice. In this article, we describe and discuss the pedagogical questions "what, why, and how" of teaching pharmacology to undergraduate veterinary nurses implemented in the Veterinary Nursing programme in Sweden. The program has undergone vast changes with classes increasing from 40 to 120 students during the last decade. The progression in the program is presented as intended learning objectives, the teaching and learning activities, and the assessment tasks in each course concerning pharmacology. The procedure of several student-activating pedagogical methods is presented. The use of students' evaluations to assess the education, in line with student-centered education, is described. This information can be useful for veterinary nursing program directors, course leaders, administrators, or teachers considering undertaking curricular changes.

Mastitis is the most burdensome concern for the dairy cattle industry. Antimicrobials are often prophylactically administered to dairy cows at dry-off to reduce the risk of intramammary infection during the dry period and subsequent lactation. Mastitis incidence has increased in dairy heifers after calving, leading to extralabel drug use of various dry cow products, including intramammary ceftiofur hydrochloride. However, the pharmacokinetics and efficacy of this application have yet to be studied. This study aimed to compare the pharmacokinetics and efficacy following no treatment, a non-antimicrobial teat sealant, or a single dose of intramammary ceftiofur given at 21 or 14 days before expected calving. We hypothesized that milk collected following dosing would contain drug residues below the FDA tolerance of 100 ng/mL by calving, and heifers within the ceftiofur treatment groups would have lower somatic cell counts (SCCs) than heifers in the teat sealant and nontreatment control groups. Following treatment or no treatment of 24 prepartum heifers, milk samples were collected until 21 days after calving. Somatic cell counts and ceftiofur concentrations were assessed utilizing a cell counter and UPLC/MS detection, respectively. Ceftiofur administration did not significantly reduce SCCs compared to other groups by days 7, 14, or 21. For heifers treated 14 and 21 days prior to calving, milk had a maximum ceftiofur concentration of 8.14 ± 6.24 and 4.20 ± 5.07 ng/mL 48 h into lactation, respectively. The minimal ceftiofur concentrations in milk collected from these heifers indicate that administration of ceftiofur 14 or 21 days before calving is unlikely to lead to violative residues. However, it is essential that regional regulations regarding the use of ceftiofur are adhered to.

Our aim was to investigate whether vatinoxan, a peripherally acting alpha₂-adrenoceptor antagonist, would affect the concentrations of medetomidine, midazolam, and fentanyl in the central nervous system after subcutaneous co-administration. Twelve healthy male Wistar rats, aged between 13 and 15 weeks, were used in this study. The animals received one of two subcutaneously administered treatments: medetomidine 0.25 mg/kg, midazolam 2 mg/kg, and fentanyl 0.01 mg/kg (MMF) or MMF with 5 mg/kg of vatinoxan (MMF-V). 15 min later, the sedated rats were humanely euthanized with intravenous pentobarbital. Plasma and tissue, including aliquots of the cortex, thalamus, pons, and lumbar spinal cord, were harvested and analyzed for drug concentrations. The treatments were compared with Bonferroni corrected t-tests after one-way analysis of variance. The concentrations of medetomidine (144 ± 19.4 vs. 107 ± 13.1 ng/g [mean ± 95% confidence interval]) (p = 0.04) and fentanyl (2.3 ± 0.2 vs. 1.7 ± 0.3 ng/g) (p = 0.04) in the cortex were significantly higher in the rats administered MMF-V. Similarly, cortex: plasma drug concentration ratios were significantly higher for medetomidine, midazolam, and fentanyl after MMF-V (p < 0.001 for all). The results confirm that vatinoxan increases early cortical exposure to subcutaneously co-administered medetomidine and fentanyl.

This meta-analysis provides a population model of doxycycline (DOXY) disposition in pigs for computation of PK/PD cutoff values corresponding to differing modalities of DOXY administration orally in pigs. This analysis enables establishment of specific clinical breakpoints for the development of antimicrobial susceptibility testing of DOXY in pigs. The meta-analysis of 380 data sets, totaling 3295 plasma concentrations obtained from 300 pigs weighing 8.5–101 kg, was performed using a non-linear mixed effect model. The plasma clearance for a typical 50 kg BW pig was estimated to be 0.259 L/kg/h with a corresponding plasma half-life of 7.33 h. The bioavailability of DOXY administered in feed under field conditions was estimated to be 50%, with a large between-subject variability of 84.8%. The bioavailability of DOXY in solution in drinking water was significantly lower (30.7%) but much less variable, with a between-subject variability of 34.3%. Several dosing schedules (5 to 20 mg/kg per day) for two administration modalities (drinking water vs. food) were simulated to calculate the corresponding PK/PD cutoffs. The highest PK/PD cutoff of 0.50 mg/L was obtained for DOXY administered in feed at 20 mg/kg BW.