Journal of veterinary pharmacology and therapeutics最新文献

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.

Isavuconazole, a triazole antifungal used in humans for invasive fungal infections, may be effective for treating canine fungal infections, although data on its use in dogs is limited. This study aimed to determine the pharmacokinetics and safety of a single dose of isavuconazole in dogs, administered both intravenously and orally. Six healthy dogs received 186 mg isavuconazonium sulfate in a crossover design, with blood samples collected over 28 days and an 8-week washout period. Plasma isavuconazole and isavuconazonium concentrations were measured by liquid chromatography/mass spectrometry, and pharmacokinetic parameters were determined by non-compartmental analysis. Isavuconazole was well tolerated, with key findings including intravenous clearance at 350 ± 112 mL/kg/h, volume of distribution at steady state at 9.8 ± 4.5 L/kg, and a terminal half-life of 90 ± 44 h. For oral administration, the maximum concentration was 0.60 ± 0.27 μg/mL, time to maximum concentration was 6.73 ± 2.45 h, terminal half-life was 125 ± 80 h, and the area under the curve was 7.44 ± 2.39 μg h/mL. Oral bioavailability was 81.4% ± 12.8%. These results suggest isavuconazole has a long half-life in dogs and is well absorbed orally when administered in the fasted state. Further studies are warranted to establish a therapeutic regimen in dogs.

Thiafentanil is a popular opioid agonist used for wildlife chemical immobilisation. Its effects are quickly and completely reversed by the antagonist naltrexone. Successful wildlife immobilisations using thiafentanil have been documented in a variety of wildlife species globally. The aim of this study was to describe the single-dose intramuscular (IM) and intravenous (IV) pharmacokinetics of thiafentanil in goats at a dose of 90 μg/kg using a single cross-over study. The IM dose was administered in the left Vastus lateralis. Plasma samples were collected up to 120 min after thiafentanil administration from two female and eight male adult goats. Samples were analysed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Pharmacokinetic parameters from one and two-compartment models were estimated via a Bayesian approach. The two-compartment model was preferred overall. The estimated bioavailability was 0.677 (90% Crl: 0.542–0.888), absorption rate constant (k_a) was 0.058 1/min (90% Crl: 0.045–0.115) and clearance was 29.0 mL/min/kg (90% Crl: 23.7–36.3) from this model. This study provides key pharmacokinetic data on thiafentanil, supporting a two-compartment model and offering insights into its absorption, bioavailability, and clearance when used for wildlife immobilisation.

This special issue of Journal of Veterinary Pharmacology and Therapeutics was precipitated by the launch of SGLT2-inhibitors onto the veterinary market for the treatment of diabetes mellitus in cats. It is hard to overstate the significance of a novel oral mode of treatment for diabetes given that a practitioner survey found that 1 in 10 owners will euthanise their pet because of not wanting to inject insulin (Niessen et al. 2017). As Drs Cook and Berend comprehensively discuss in this issue of JVPT, cats are well suited to treatment with SGLT-inhibitors because unlike dogs many have some residual β-cell function (Cook and Behrend 2025). These drugs may also be valuable in the management of insulin dysregulation that is a central feature of equine metabolic syndrome and the associated problem, equine laminitis, for which there are currently no licensed treatments (Menzies-Gow and Knowles 2025).

Now that SGLT2-inhibitors have been brought to the veterinary market it seems opportune to consider the potential of their wider use in treatment of renal and cardiovascular disease in veterinary patients (Elliott and Oyama 2025). The interest in their use for these indications stems from the evidence from human medicine that treatment with this class of drugs (and it does seem to be a class effect rather than being associated with any individual drug) reduces the risk of major cardiac adverse events and slows the rate of progression of diabetic kidney disease. Following these discoveries the clinical indications for these drugs have been expanded to include management of various forms of non-diabetic kidney and cardiac diseases, stemming in part from the observation that SGLT2-inhibitors actual benefits were greater in diabetic patients than would be anticipated just from the relatively mild weight loss and decrease in blood pressure.

Given the explosion in potential indications for these drugs, and the excitement surrounding their potential benefit for humans especially considering the current obesity epidemic with all its serious medical sequelae, it is easy to overlook the fact that these positive health effects were not anticipated. In fact, the huge trials that were performed with SGLT2-inhibitors were FDA-mandated studies required following the launch of any new glucose-lowering treatment due to concern that their use might be associated with ADVERSE cardiac outcomes (Udell et al. 2015). Indeed, the finding that SGLT2-inhibitors were not detrimental, but actually improved outcomes, was really quite unexpected (Zinman et al. 2015).

As a veterinary clinical researcher, it is possible to get quite despondent when looking at these clinical trials in humans, with the feeling that nothing on a comparable scale will ever be possible in veterinary patients. For example, a recent meta-analysis of the risk of reaching a composite end-point of End Stage Kidney Di