Journal of veterinary pharmacology and therapeutics最新文献

{"title":"Single-Dose, Intravenous, and Oral Pharmacokinetics of Isavuconazole in Dogs.","authors":"Yishan Kuo, Zhong Li, Lauren E Forsythe, Jennifer M Reinhart","doi":"10.1111/jvp.13510","DOIUrl":"https://doi.org/10.1111/jvp.13510","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Bioavailability of Single-Dose Intramuscular and Intravenous Administration of Thiafentanil in Goats (Capra hircus).","authors":"Judith T Christie, Mieghan Bruce, Silke Pfitzer, Liesel Laubscher, Jacobus P Raath, Michael Laurence, Tracy Kellermann, Andrew P Woodward","doi":"10.1111/jvp.13507","DOIUrl":"https://doi.org/10.1111/jvp.13507","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiparasitic Collars: Concentration Levels of Imidacloprid and Flumethrin in Dog Fur Suggest Low Toxicity Risks for Adult Humans.","authors":"Margaux Buisson, Laurine Dumas, Célia Gouffran, Eloïse C Déaux, Laurent Rougier, Sylvia Masson","doi":"10.1111/jvp.13508","DOIUrl":"https://doi.org/10.1111/jvp.13508","url":null,"abstract":"<p><p>Seresto by Elanco (formerly Bayer Animal Health) is a collar for cats and dogs that provides long-lasting antiparasitic protection through the gradual release of imidacloprid and flumethrin onto the animal's skin. Although the EPA has deemed Seresto safe, their assessment is based on laboratory data, which may not fully reflect real-world exposure. Furthermore, recent reports of over 900 adverse human health events between 2012 and 2022 underscore the need for further safety investigations. We measured these chemicals' concentrations from the fur of eight dogs over 9 months to evaluate how daily interactions with pets could expose humans to toxic levels. Flumethrin was mostly undetectable, and imidacloprid levels were well below the toxicity threshold, suggesting low risks. However, factors like cumulative exposure and individual characteristics warrant consideration. Concentration levels were highest right after collar application, potentially reaching up to 11.6% of an 8 kg child's acceptable daily intake. We recommend limiting prolonged contact with pets, especially for young children, in the first 48 h post-application. We detected residual imidacloprid prior to collar application and 1 month after removal, raising questions as to the potential contamination risks that roaming pets could pose to ecosystems, given the known environmental impacts of these chemicals.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Ampicillin-Sulbactam in Azotemic and Non-Azotemic Dogs.","authors":"Zhe Wang, Sarah Shropshire, Daniel Gustafson, Samantha Fedotova, Amanda Diaz, Nida Chornarm, Joshua B Daniels, Jessica Quimby, Kristin M Zersen","doi":"10.1111/jvp.13506","DOIUrl":"https://doi.org/10.1111/jvp.13506","url":null,"abstract":"<p><p>Previous research has shown that azotemic dogs have a lower clearance and higher drug plasma concentrations of ampicillin compared to healthy dogs. The objective of this study was to determine the pharmacokinetics of ampicillin-sulbactam after multiple intravenous doses in hospitalized azotemic and non-azotemic dogs. This prospective study included 29 client-owned dogs; 19 azotemic and 10 non-azotemic. Ampicillin-sulbactam was administered at a combined dose of 22 mg/kg intravenously every 8 h for up to 5 days. Blood samples were obtained at baseline (prior to administration of the first dose of ampicillin-sulbactam), and 1-, 4-, and 8-h post-ampicillin-sulbactam administration each day. Plasma ampicillin was measured using LC-MS and non-compartmental pharmacokinetic modeling and dose interval modeling were performed. Plasma ampicillin exposure (azotemic mean 214.5 ug/mL × h ± 110.8, non-azotemic mean 60.3 ± 35.7; p < 0.0009) and half-life (azotemic mean 3.9 h ± 2.4, non-azotemic mean 1.5 h ± 0.3; p < 0.00001) were statistically greater in azotemic dogs compared to non-azotemic dogs. Single dose interval modeling predicted that 100% of azotemic dogs would have > 50% of the dosing interval with plasma concentrations > MIC (MIC = 2) with q12 h dosing and 79% of azotemic dogs would have > 50% of the dosing interval with plasma concentrations > MIC (MIC = 8) with q12 h dosing. Comparatively, 20% of non-azotemic dogs were predicted to have > 50% of the dosing interval with plasma concentrations > MIC (MIC = 2) with q12 h dosing and 0 non-azotemic dogs would have > 50% of the dosing interval with plasma concentrations > MIC (MIC = 8) with q12 h dosing. This study demonstrated that q12-h dosing of ampicillin-sulbactam in azotemic dogs over multiple days of administration is sufficient to reach the PK-PD target (> 50% of dosing interval > MIC) against susceptible bacteria.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Look and you Will Find it—What is Unsought Will go Undetected.” Sophocles","authors":"Harriet M. Syme,&nbsp;Jonathan Elliott","doi":"10.1111/jvp.13502","DOIUrl":"10.1111/jvp.13502","url":null,"abstract":"&lt;p&gt;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. &lt;span&gt;2017&lt;/span&gt;). 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 &lt;span&gt;2025&lt;/span&gt;). 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 &lt;span&gt;2025&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;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 &lt;span&gt;2025&lt;/span&gt;). 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.&lt;/p&gt;&lt;p&gt;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. &lt;span&gt;2015&lt;/span&gt;). Indeed, the finding that SGLT2-inhibitors were not detrimental, but actually improved outcomes, was really quite unexpected (Zinman et al. &lt;span&gt;2015&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;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","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 2","pages":"65-66"},"PeriodicalIF":1.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis and Mechanism-Based Modeling of Synovial and Plasma Pharmacokinetics and Adrenal Suppression Following Intra-Articular Injection of Methylprednisolone Acetate in Horses.","authors":"Ruihong Yu, William J Jusko","doi":"10.1111/jvp.13504","DOIUrl":"https://doi.org/10.1111/jvp.13504","url":null,"abstract":"<p><p>This study assesses the pharmacokinetics (PK) of published methylprednisolone (MPL) data in horses following intra-articular (IA) administration of MPL acetate (MPA) and the associated adrenal suppression. The concentrations of MPL/MPA in synovial fluid, blood, and urine, as well as hydrocortisone (HC) in plasma, were digitized from multiple sources in the literature. A minimal physiologically based pharmacokinetic model and a linked indirect response model with a circadian rhythm baseline were applied. Concentrations of MPA in joints followed a triexponential decay, converting to MPL. The clearance of MPL was 797 mL/h/kg via hepatic metabolism (93%) and renal excretion (7%). The persistence of MPL in synovium and plasma for over 500 h was primarily ascribed to slow prodrug dissolution. The formation of MPL from available MPA in SF was rapid. A transit step was needed between the synovium and plasma for MPL absorption. The MPA to MPL bioavailability was dose and/or study dependent; 100% for dosages below 100 mg and 58% for 200 mg. The MPL inhibition of HC production was potent, with an IC₅₀ of 0.83 ng/mL, and lasted over 50 h. This meta-analysis utilizing a mechanistic modeling approach provided advanced and comprehensive insights on IA MPL PK in horses and was translatable for the PK appreciation of IA MPA dosing in man.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Residue Behavior and Risk Assessment of Diazepam and Its Metabolites in Crucian Carp (Carassius auratus) After Oral Administration.","authors":"Qi Shan, Xiaosheng Huang, Shucai Ye, Hao Zhou, Feng Xu, Jianqiang Li, Jiawei Lin, Lichun Li, Yi Yin","doi":"10.1111/jvp.13505","DOIUrl":"https://doi.org/10.1111/jvp.13505","url":null,"abstract":"<p><p>Diazepam (DZP), a benzodiazepine medication, is extensively utilized in both human and veterinary medicine and has been frequently detected in fish populations. The use of DZP-laced bait is identified as a predominant contributor to drug residue contamination in fish. Nonetheless, our understanding of the residue profile of DZP in fish and its potential implications for human health remains constrained. This study investigated the residue behavior and dietary intake risks of DZP and its primary metabolites in crucian carp (Carassius auratus) following oral administration. A rapid and sensitive UHPLC-MS/MS method was developed and validated for the reliable quantification of DZP and its identified metabolites. The findings revealed rapid absorption and extensive distribution of DZP in crucian carp, with peak concentrations in plasma and tissues occurring at 1 h. The distribution pattern of DZP, based on calculated AUC, was kidney > liver > plasma > gill > muscle plus skin. The distribution of DZP in plasma and tested tissues followed the decreasing order of kidney > liver > plasma > gill > muscle plus skin according to the calculated AUC. DZP elimination was notably slow, particularly in muscle plus skin, with an elimination half-life of 619.31 h, necessitating at least 70 days for concentrations to fall below the limit of quantitation, suggesting a high likelihood of residue formation in fish from oral DZP administration. DZP was metabolized into nordiazepam and temazepam in crucian carp; nordiazepam is the main metabolite of DZP, which is gradually higher than the parent drug in the elimination phase. The dietary risk assessment suggested that a possible health risk (HQ ≥ 0.1) was found within 1 day via ingestion of crucian carp after an oral dose of DZP, suggesting that frequent consumption of high-residue crucian carp may cause harm to human health.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of the Selective JAK1 Inhibitor Oclacitinib in Dogs.","authors":"Steven M Nederveld, Matthew J Krautmann, John Mitchell","doi":"10.1111/jvp.13503","DOIUrl":"https://doi.org/10.1111/jvp.13503","url":null,"abstract":"<p><p>Apoquel(oclacitinib maleate) as a film-coated tablet, a selective Janus kinase (JAK)1 inhibitor, was approved by the United States Food and Drug Administration (FDA) in 2013 for the control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age. The goal of this review is to describe the safety of oclacitinib in dogs based on data from investigational laboratory and field studies, independent directed studies, and an extensive postmarketing pharmacovigilance (PV) surveillance program. The safety of oclacitinib has been extensively evaluated in investigational and independent studies. In the oclacitinib postapproval PV surveillance, the types and rank order of frequency of reported adverse events were similar to the premarketing field studies, with diarrhea, anorexia, and lethargy being the most frequently reported adverse events. In the postmarketing PV continuous monitoring, adverse events for patients receiving oclacitinib are rarely reported and the individual clinical signs within the PV adverse event reports were considered \"very rare\" in frequency. An age- and breed- matched retrospective cohort study in dogs with allergic dermatitis showed no significant difference in incidence of neoplasia between dogs treated with oclacitinib and dogs treated with other systemic therapies. The extensive investigational and PV experience with oclacitinib shows that long-term or lifelong use per label instructions has a positive benefit-risk profile and is not associated with any cumulative safety risk.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patrick De Backer—Obituary","authors":"Siska Croubels,&nbsp;Mathias Devreese","doi":"10.1111/jvp.13501","DOIUrl":"10.1111/jvp.13501","url":null,"abstract":"","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"48 2","pages":"133"},"PeriodicalIF":1.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma and Urine Pharmacokinetics of Long-Acting Injectable Omeprazole Following Intramuscular Administrations to Healthy Thoroughbred Horses.","authors":"Caitlin Harding, Marjaana Viljanto, Pamela Hincks, Jocelyn Habershon-Butcher, Stuart W Paine","doi":"10.1111/jvp.13494","DOIUrl":"https://doi.org/10.1111/jvp.13494","url":null,"abstract":"<p><p>Omeprazole is a gastric acid secretion inhibitor used as an effective anti-ulcer drug. Based on oral administration studies, its International Screening Limit (ISL) was established in plasma and urine at 1 ng/mL with a Detection Time (DT) of 48 h. A novel formulation of injectable omeprazole has since been released, and therefore, a pharmacokinetic study was performed to assess the DT above the ISL against current advice. Six Thoroughbred horses were given four repeated weekly intramuscular administrations of omeprazole (4 mg/kg). Plasma and urine omeprazole concentrations were measured by liquid chromatography-tandem mass spectrometry. Based on the current plasma and urine ISL (1 ng/mL), the DT for this long-acting omeprazole formulation administered at 4 mg/kg once per week is greater than 384 h (16 days) in both plasma and urine. Thus realistically, despite the appeal of giving an injection once per week rather than oral medication daily over a long period of time, this would make treatment for horses in training with the long-acting product challenging within the rules of racing. It would therefore most likely be used for horses outside of training, and the oral formulation would still be legitimately used during training.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}