Journal of veterinary pharmacology and therapeutics最新文献

{"title":"Factoring fu Variability Into Estimates of Unbound Drug Concentrations Negatively Biases the MIC Versus % Probability of Target Attainment Relationship of Antimicrobial Agents.","authors":"Marilyn N Martinez, Mark G Papich, Pierre-Louis Toutain","doi":"10.1111/jvp.13498","DOIUrl":"https://doi.org/10.1111/jvp.13498","url":null,"abstract":"<p><p>The clinical breakpoint for a drug-pathogen combination reflects the drug susceptibility of the pathogen wild-type population, the location of the infection, the integrity of the host immune response, and the drug-pathogen pharmacokinetic (PK)/pharmacodynamic (PD) relationship. That PK/PD relationship, along with the population variability in drug exposure, is used to determine the probability of target attainment (PTA) of the PK/PD index at a specified minimum inhibitory concentration (MIC) for a selected target value. The PTA is used to identify the pharmacodynamic cutoff value (CO_PD), which is one of the three components used to establish the clinical breakpoint. A challenge encountered when defining the CO_PD is that the available PK information typically reflects total (free plus protein-bound) plasma concentrations. However, it is the unbound drug concentrations that exert the therapeutic effects and how the population fraction unbound (fu) incorporated into the CO_PD assessments can markedly influence the CO_PD. Factors examined included the estimated population fu mean (risk of bias) and the incorporation of estimated fu population variability into the Monte Carlo simulations when converting total to unbound plasma concentrations (risk of inflating variability). In this in silico study, the drug fu, systemic clearance, and the variability of both were altered so that the relative impact of each could be explored. We demonstrate that incorporating fu variability into the estimation of fAUCback can bias the CO_PD assessment and that the magnitude of bias reflects the relative variability in systemic clearance and fu.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033421","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":"Biosafety and Withdrawal Period of In-Feed Administered Antiparasitic Drug Emamectin Benzoate in Cirrhinus mrigala (Hamilton, 1822).","authors":"H G Solanki, A Verma, H K Solanki, R A Raja, S Avunje, B J Trangadia, S K Panda, P K Patil","doi":"10.1111/jvp.13495","DOIUrl":"https://doi.org/10.1111/jvp.13495","url":null,"abstract":"<p><p>Parasitic infestations are one of the most economically important disease conditions in the Indian major carps including mrigal, Cirrhinus mrigala. This study reported the biosafety and tissue withdrawal of in-feed administered antiparasitic drug, emamectin benzoate (EMB). To evaluate the biosafety of the drug, behaviour, growth and tissue changes in Cirrhinus mrigala was recorded the following in-feed administration of EMB up to 10 times (T1-50 μg kg^-1 fish day^-1 (1×), T2-125 μg kg^-1 fish day^-1 (2.5×), T3-250 μg kg^-1 fish day^-1 (5×), T4-375 μg kg^-1 fish day^-1 (7.5×) and T5-500 μg kg^-1 fish day^-1 (10×)) for the period of three times the recommended duration (7 days). The withdrawal period was calculated by feeding EMB at 50 μg kg^-1 fish day^-1 for consecutive 10 days followed by EMB-free feed. The results revealed that the drug is safe to mrigal up to ten times the recommended dose, while the fish fed with the highest dose (500 μg kg^-1 fish day^-1) showed transient histological alterations. The feeding behaviour is affected with poor acceptability beyond 5× dosages. The drug residue at the concentration below the MRL (1.0 μg g^-1) in the muscle tissue on the day of cessation of medicated feed administration indicates no requirement of the withdrawal period. The study suggests that EMB can be safely used at 50 μg kg^-1 fish day^-1 for 7 consecutive days, and no withdrawal period is required without affecting the feeding behaviour and tissue histological alterations.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007720","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":"Population Pharmacokinetics of Enrofloxacin in Ctenopharyngodon idella Based on the Sparse Sampling Method and a Nonlinear Mixed Effect Model Following Intravenous and Oral Administration.","authors":"Ning Xu, Huan Zhang, Shun Zhou, Yongtao Liu, Qiuhong Yang, Jing Dong, Yongzhen Ding, Xiaohui Ai","doi":"10.1111/jvp.13497","DOIUrl":"https://doi.org/10.1111/jvp.13497","url":null,"abstract":"<p><p>The objective of this study was to implement population pharmacokinetic (PPK) of enrofloxacin (EF) in grass carp (Ctenopharyngodon idella) after a single oral administration and a single intravenous administration based on a nonlinear mixed effect model. The plasma samples collected by the sparse sampling method were detected by high-performance liquid chromatography with a fluorescent detector. The initial pharmacokinetic (PK) parameters were evaluated by reference search and the calculation of a naïve pooled method. After oral administration, the concentration-time profile was best described by a one-compartment open model. The absorption rate constant (K_a), apparent distribution volume (V), and systemic clearance (CL) were estimated to be 3.11/h, 4.36 L/kg, and 0.079 L/h/kg, respectively. After intravenous administration, the concentration-time curve was best simulated by a two-compartment open model. The apparent distribution volume of the central compartment (V₁), apparent distribution volume of the peripheral compartment (V₂), CL, and clearance from the central compartment to the peripheral compartment (CL₂) were estimated to be 0.42, 2.05 L/kg, 0.067, and 2.94 L/h/kg, respectively. Finally, the bioavailability was calculated to be 84.81%. The parameter of AUC/minimum inhibitory concentration value was estimated to be more than 506.32 for Aeromonas hydrophila, Aeromonas sobria, and Flavobacterium columnare indicating that EF at 20 mg/kg has high effectiveness for these pathogens. This study supported a concise method for conducting PK study in aquatic animals that facilitated the development of PK methodology in aquaculture.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971461","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 Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses.","authors":"Peter Michanek, Johan Bröjer, Inger Lilliehöök, Cathrine T Fjordbakk, Minerva Löwgren, Mikael Hedeland, Jonas Bergquist, Carl Ekstrand","doi":"10.1111/jvp.13476","DOIUrl":"10.1111/jvp.13476","url":null,"abstract":"<p><p>Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, 1.33, 1.66, 2, 2.33, 2.66, 3, 3.5, 4, 5, 6, 8, 12, 24, 32, and 48 h post administration. CFZ was quantified using UHPLC coupled to tandem quadrupole mass spectrometry (UHPLC-MS/MS). A non-compartmental analysis revealed key pharmacokinetic parameters, including a median T_max of 7 h, a C_max of 2350 ng/mL, and a t_1/2Z of 28.5 h. CFZ treatment reduced glucose (AUC_GLU, p = 0.001) and insulin (AUC_INS, p = 0.04) response to a graded glucose infusion administered 5 h after treatment. This indicates a rapid onset of action following a single dose in healthy Icelandic horses. No obvious adverse effects related to the treatment were observed.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":"41-49"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902186","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":"Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses.","authors":"Nicola J Menzies-Gow, Edward J Knowles","doi":"10.1111/jvp.13470","DOIUrl":"10.1111/jvp.13470","url":null,"abstract":"<p><p>Laminitis is a common and painful condition of the equine foot and approximately 90% of cases are associated with insulin dysregulation (ID) that is a central feature of the common endocrine disorder equine metabolic syndrome (EMS) and occurs in a subset of animals with pituitary pars intermedia dysfunction. Additional features of EMS include obesity, altered circulating concentrations of adipokines (particularly adiponectin and leptin) and hypertriglyceridaemia. Obesity, ID, hypoadiponectinaemia, hyperleptinaemia and an altered plasma lipid profile are also features of human metabolic syndrome (HMS) alongside hyperglycaemia. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycaemic agents used in combination with lifestyle changes in the management of HMS. SGLT2 receptors are responsible for 90% of the renal glucose reabsorption that occurs in the proximal convoluted tubule. Thus, these drugs increase urinary glucose excretion by suppressing glucose reabsorption from the glomerular filtrate resulting in urinary calorie loss with consequent weight loss and improvements in ID, hyperglycemia, hypoadiponectinaemia and hyperleptinaemia. There are no licenced veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses. Thus, the use of SGLT2i for the control of equine hyperinsulinaemia with the goal of improving recovery from associated active laminitis or preventing future laminitis has recently been advocated. There are a small number of published studies reporting the use of the SGLT2i canagliflozin, ertugliflozin and velagliflozin to aid the management of equine ID. However, the doses used are largely extrapolated from human studies with limited consideration of species-specific variations. In addition, there is limited evaluation of the fundamental differences between ID in horses and humans, particularly the fact that most horses with ID remain hyperinsulinaemic but normoglycaemic such that increased urinary loss of glucose may not explain the beneficial effects of these drugs. Further study of the potential deleterious effects of treatment-associated hypertriglyceridaemia is required together with the effect of SGLT2i therapy on circulating concentrations of adipokines in horses.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":"31-40"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563661","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":"SGLT2 inhibitor use in the management of feline diabetes mellitus.","authors":"Audrey K Cook, Ellen Behrend","doi":"10.1111/jvp.13466","DOIUrl":"10.1111/jvp.13466","url":null,"abstract":"<p><p>Sodium-glucose cotransporter-2 (SGLT2) inhibitors are routinely used in the management of human type 2 diabetes and have been shown to effectively mitigate hyperglycemia and reduce the risks of cardiovascular and renal compromise. Two SGLT2 inhibitors, namely bexagliflozin and velagliflozin, were recently FDA approved for the treatment of uncomplicated feline diabetes mellitus. These oral hypoglycemic agents are a suitable option for many newly diagnosed cats, with rapid improvements in glycemic control and clinical signs. Suitable candidates must have some residual β-cell function, as some endogenous insulin production is required to prevent ketosis. Appropriate patient selection and monitoring are necessary, and practitioners should be aware of serious complications such as euglycemic diabetic ketoacidosis.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":"19-30"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492495","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":"Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases?","authors":"Jonathan Elliott, Mark A Oyama","doi":"10.1111/jvp.13472","DOIUrl":"10.1111/jvp.13472","url":null,"abstract":"<p><p>Sodium glucose transporter type 2 (SGLT2) inhibitors have been introduced into human medicine where their beneficial effects go beyond the expected improvement in blood glucose control. These drugs appear to prevent progression of both cardiovascular and kidney diseases, not only in diabetic but also in non-diabetic human patients. As these drugs have received conditional approval for use in diabetic cats and are being used in other veterinary species, the intriguing question as to whether they will have similar cardioprotective and nephroprotective effects in dogs and cats is being asked. The primary mechanism(s) by which SGLT2 inhibitors are cardio- and nephroprotective remain to be fully characterized. This paper reviews these suggested mechanisms in the context of the pathophysiology of progressive cardiovascular and kidney diseases in dogs and cats with the goal of predicting which categories of non-diabetic veterinary patients these drugs might be of most benefit.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":"1-18"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600313","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":"Analysis of US Marketed Artemisinin Supplements for Use in Dogs.","authors":"Alyssa R Berman, Adam J Birkenheuer, Emily L Sorah, Mark G Papich","doi":"10.1111/jvp.13480","DOIUrl":"10.1111/jvp.13480","url":null,"abstract":"<p><p>Oral artemisinin has antiparasitic activity and may help improve treatment success rates in dogs infected with Babesia gibsoni. However, these artemisinin products are unapproved and unregulated botanical supplements. They have not been evaluated for safety and efficacy or for strength, purity, or quality compared with a reference standard. Before considering these products for a clinical study, we evaluated the strength of four suppliers of artemisinin capsules using an high-performance liquid chromatography method validated in our laboratory. We found that the four artemisinin-labeled products that were tested had high within product and between product variability in capsule strength compared with the stated capsule strength on the product label. No products met the acceptance criteria of the United States Pharmacopeia and International Council for Harmonisation (ICH) as well as the criteria adapted by the authors. One product had no detectable artemisinin, and the other three products were much higher than the stated label strength. The results of this study reinforce the importance of testing unapproved and unregulated supplements before recommending a supplement for clinical use in dogs.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":"56-60"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046854","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":"Efficacy of Procaine, With and Without Epinephrine, Compared to Lidocaine in Local Anesthesia for Calves Before Thermocautery Disbudding.","authors":"Magdy Adam, Annemari Jokela, Kati Salla, Riikka Aho, Marja Raekallio, Laura Hänninen, Ann-Helena Hokkanen","doi":"10.1111/jvp.13493","DOIUrl":"https://doi.org/10.1111/jvp.13493","url":null,"abstract":"<p><p>Within the European Union, the use of lidocaine in food-producing animals is restricted due to concerns over human safety. This study compared the clinical effectiveness of procaine, with and without epinephrine, against lidocaine in pain alleviation during thermocautery disbudding in xylazine-sedated calves. The efficacy of local blocks was assessed through needle pricks, and the behavioral reactions to disbudding were scored. Post-disbudding pain was subjectively evaluated, and pressure pain threshold and tactile sensitivity around the horn bud were assessed at intervals. Blood was collected at intervals for plasma cortisol analysis. No significant differences were found between the groups in the needle prick test (p = 0.329) and the disbudding score (p = 0.855). Pain scores and quantitative sensory tests showed no significant differences between the lidocaine and procaine-epinephrine groups. Conversely, tactile sensitivity and pain scores were significantly higher, and pressure pain thresholds were significantly lower with procaine alone than in other groups. Elevated cortisol concentrations were observed in all groups before disbudding compared to the baselines. The results suggest that procaine combined with epinephrine appears to be a safe and effective alternative to lidocaine for calf disbudding. Cortisol concentrations as an indicator of pain in xylazine-sedated calves appear inadequate.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729778","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":"The Single-Dose Pharmacokinetics of a Compounded Levetiracetam Formulation and Bioequivalence to a Commercial Formulation in Healthy Dogs.","authors":"Aaron M Paushter, Kari D Foss, Jennifer M Reinhart, Lauren E Forsythe, Devon W Hague","doi":"10.1111/jvp.13490","DOIUrl":"https://doi.org/10.1111/jvp.13490","url":null,"abstract":"<p><p>Levetiracetam (LEV) is an anti-epileptic drug used extra-label in dogs. Commercially available extended-release formulations (LEV-ER), administered twice daily, cannot be crushed or split, limiting their use in small dogs. A compounded LEV-ER formulation (PO-COMP) can purportedly be partitioned without loss of extended-release properties. The aims of this study were to establish the pharmacokinetic parameters of PO-COMP, divided at the tablet score, and determine the bioequivalence of partitioned PO-COMP to an intact commercially available Food and Drug Administration-approved human oral generic formulation of LEV-ER (PO-COMM). In a randomized crossover design, 12 healthy dogs received a single IV dose (30 mg/kg) of IV-COMM, a single oral dose (500 mg) of intact PO-COMM, or a single oral dose (500 mg) of partitioned PO-COMP and underwent serial measurement of plasma LEV concentrations over 24 h. PO-COMP was bioequivalent to PO-COMM using the 90% confidence interval method for maximum concentration (-3.2% difference [CI -7.4% to -1.1%]) and area under the curve (-14.4% difference [CI -17.8% to 10.8%]). PO-COMP may improve medication adherence and seizure control relative to immediate-release LEV, which requires three times daily dosing. Efficacy studies of PO-COMP are warranted.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622816","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}