Journal of veterinary pharmacology and therapeutics最新文献

{"title":"Pharmacokinetics, Safety Assessment and Residue Kinetics of Emamectin Benzoate in Rainbow Trout, Oncorhynchus mykiss (Walbaum, 1792)","authors":"Richa Pathak,&nbsp;Neetu Shahi,&nbsp;Prasanna Kumar Patil,&nbsp;Krishna Kala,&nbsp;Niladri Sekhar Chatterjee,&nbsp;Ranjit Kumar Nadella,&nbsp;Kishor Kunal,&nbsp;Abhay Kumar Giri,&nbsp;Sumanta Kumar Mallik","doi":"10.1111/jvp.70068","DOIUrl":"10.1111/jvp.70068","url":null,"abstract":"<div>\u0000 \u0000 <p>Emamectin benzoate (EB) is widely used in aquaculture to control ectoparasites. The study evaluated the pharmacokinetics, biosafety, and muscle residue depletion of EB. In pharmacokinetics, following administration of a single oral dose of 50 μg/kg EB, plasma and tissues (liver, kidney, gill, intestine, and muscle) were sampled up to 128 h and analysed using LC–MS/MS. EB showed tissue-specific distribution, with the highest <i>C</i>_max (565 μg/kg) and AUC (35,927.69 μg·h/kg) in kidney, and lowest <i>C</i>_max (13.07 μg/kg) and AUC (368.40 μg·h/kg) in muscle. The intestine exhibited the longest half-life (648.33 h), indicating prolonged retention. Biosafety was assessed at 1× (50 μg/kg), 5× (250 μg/kg), and 10× (500 μg/kg) doses for 21 days. Fish tolerated the therapeutic dose (1×) without behavioural abnormalities, while higher doses (5× and 10×) caused dose-dependent pigmentation, reduced feed intake, and histopathological alterations in major organs. Muscle residues remained below the MRL (100 μg/kg) at the 1× dose. It declined below the MRL by day 21 in the 5× group, and reached below the MRL only by day 14 post-dosing in the 10× group. These findings support the safe use of EB at recommended levels in rainbow trout, while higher doses increase toxicity and residue persistence.</p>\u0000 </div>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 5","pages":"548-563"},"PeriodicalIF":1.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486423","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 Moxidectin in Bare-Nosed Wombats (Vombatus ursinus) After Intravenous, Sub-Cutaneous and Transdermal Administration","authors":"E. K. Stott,&nbsp;L. F. Skerratt,&nbsp;T. Whittem,&nbsp;M. Leeming,&nbsp;K. Pillay,&nbsp;G. S. Doran,&nbsp;B. Gardner,&nbsp;M. Lynch,&nbsp;M. Klein,&nbsp;P. Holz,&nbsp;T. Chen,&nbsp;J. Hufschmid,&nbsp;A. P. Woodward","doi":"10.1111/jvp.70074","DOIUrl":"10.1111/jvp.70074","url":null,"abstract":"<p>The anti-parasitic drug moxidectin is a frontline treatment for sarcoptic mange in bare-nosed wombats (<i>Vombatus ursinus</i>), a disease causing significant animal welfare issues and instances of local population declines. Despite widespread usage, knowledge of species-specific pharmacokinetics of moxidectin in bare-nosed wombats is still limited. This study describes the clinical pharmacokinetics of moxidectin by intravenous, subcutaneous, and transdermal routes of administration in bare-nosed wombats. Plasma moxidectin concentration was assessed by liquid chromatography mass spectrometry and analysed by Bayesian hierarchical modelling. Plasma clearance was 1.11–1.85 mL/min/kg. The subcutaneous route showed biphasic absorption, dominated by a slow terminal absorption phase (80% of the effective dose of moxidectin was absorbed in this phase) with a half-life of approximately 631 h (26.3 days). The transdermal route had an estimated half-life of 21.78 h (1308) min. The average bioavailability was 0.59% and 95.7% by the transdermal and subcutaneous route, respectively. This detailed insight into the pharmacokinetics of moxidectin in bare-nosed wombats provides a crucial foundation for the design of treatment regimens, whilst also highlighting the inefficiency of transdermal delivery.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 5","pages":"533-547"},"PeriodicalIF":1.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699152","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":"Pharmacokinetics of Diclazuril in the Plasma and Cerebrospinal Fluid of Healthy Adult Horses After a Single Oral Dose Administered as a Pelleted Topdressing","authors":"Elizabeth J. Treece,&nbsp;Kate L. Hepworth-Warren,&nbsp;Mark G. Papich,&nbsp;Philip D. van Harreveld,&nbsp;Anthony T. Blikslager,&nbsp;Faith E. Church,&nbsp;Kaitlyn B. Harbor,&nbsp;Sara J. Erwin-Craig","doi":"10.1111/jvp.70086","DOIUrl":"10.1111/jvp.70086","url":null,"abstract":"<p>Equine protozoal myeloencephalitis can cause acute infections with rapid onset of neurologic signs, necessitating immediate empiric therapy with antiprotozoal medication. The objective of the study was to identify when concentrations of diclazuril reached the MIC of <i>Sarcocystis neurona</i> in CSF (1 ng/mL) of healthy adult horses after a single oral dose. Six healthy adult horses were used. Blood and CSF were collected from indwelling intravenous jugular catheters and intrathecal catheters in the lumbosacral space prior to drug administration and then at 1-, 4-, 8-, 12-, 16-, 24-, 48-, 72-, 96-, 120-, 144-, 168-, and 192-h post-administration of a 1 mg/kg dose of pelleted diclazuril administered by mouth in 8 oz of sweet feed. Samples were centrifuged then plasma and CSF supernatant were separated and frozen at −80°C until analysis. Diclazuril concentrations were analyzed with a liquid chromatography-mass spectrometer assay developed specifically for this study. Plasma concentrations of diclazuril peaked at 48 h with a mean concentration of 395.6 ± 109.4 ng/mL. CSF concentrations of diclazuril peaked at 24 h (mean concentration 9.0 ± 5.4 ng/mL) but achieved the MIC of <i>S. neurona</i> 12 h after administration (mean concentration 2.6 ± 1.8 ng/mL) and remained above MIC for the duration of the sampling period. In conclusion, pelleted diclazuril at 1 mg/kg reaches concentrations in the CSF above the MIC for <i>S. neurona</i> in healthy horses 12 h after a single oral dose.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 5","pages":"487-496"},"PeriodicalIF":1.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147960126","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":"Influence of Tramadol on the Intravenous Pharmacokinetics of Dipyrone Active Metabolites in Dogs","authors":"Andressa Nunes Mouta,&nbsp;Kathryn Nóbrega Arcoverde,&nbsp;Robson dos Anjos Honorato,&nbsp;Naftáli Silva Fernandes,&nbsp;Caio Vinicius Almeida de Oliveira,&nbsp;Glícia Cavalcante Mesquita,&nbsp;Yanna Deysi Bandeira Passos,&nbsp;Gabriel Araújo-Silva,&nbsp;Valéria Veras de Paula","doi":"10.1111/jvp.70073","DOIUrl":"10.1111/jvp.70073","url":null,"abstract":"<p>This study aimed to compare the pharmacokinetic profile of the active dipyrone metabolites 4-methylaminoantipyrine (MAA) and 4-aminoantipyrine (AA) administered alone and in combination with tramadol in dogs. Nine mixed-breed dogs, weighing 15.33 ± 2.25 kg, participated in a two-treatment crossover design: G1 received intravenous dipyrone (25 mg kg⁻¹) and G2 received dipyrone (25 mg kg⁻¹) combined with tramadol (2 mg kg⁻¹), with a 15-day washout. Blood samples were collected up to 48 h and plasma concentrations analyzed using UPLC–MS/MS. Pharmacokinetic parameters were calculated using PKSolver 2.0. Normally distributed data were analyzed with the <i>t</i>-test, and non-normal data with the Mann–Whitney test (<i>p</i> &lt; 0.05); parameters with significant differences were subjected to Pearson correlation. Analyses were performed using Python. For MAA, Cmax and C0 differed significantly. For AA, <i>AUC</i>_0–<i>t</i>, <i>AUC</i>_0→∞, Cl, and <i>MRT</i>_0→∞ differed significantly. Tramadol and its metabolites were also described. The pharmacokinetic interaction between dipyrone and tramadol increased systemic exposure (AUC) of AA and inhibited the conversion of tramadol to M1, without direct changes in the severe adverse effects associated with MAA. Further studies involving nociceptive stimuli and multiple-dose regimens are needed to assess clinical relevance.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 5","pages":"457-470"},"PeriodicalIF":1.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775285","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":"Plasma Pharmacokinetic Profile of Fipronil 1% Pour-On in Cattle: Photodegradation and the Sustained Systemic Persistence of Fipronil Sulfone","authors":"Stefani Maria Ferreira,&nbsp;Leonila Ester Reinert Raspantini,&nbsp;Giselle Kindlein,&nbsp;Fabiano Barreto,&nbsp;Caroline Andrade Tomaszewski,&nbsp;Tamara dos Santos Castilhos,&nbsp;Daniel Rodrigo Hillesheim,&nbsp;Silvana Lima Górniak,&nbsp;André Tadeu Gotardo","doi":"10.1111/jvp.70085","DOIUrl":"10.1111/jvp.70085","url":null,"abstract":"<p>This study characterized the long-term pharmacokinetic profile of a 1% fipronil <i>pour-on</i> formulation in Nellore bulls under field conditions. Seventeen animals received a single topical dose (1 mg/kg), and plasma concentrations of fipronil and its metabolites (sulfone and desulfinyl) were monitored for 175 days using LC–MS/MS. Fipronil was rapidly absorbed, reaching a maximum concentration <i>C</i>_max of 42.3 ± 4.1 ng/mL on day 1, but became undetectable by day 35. Conversely, fipronil sulfone was the predominant systemic analyte, reaching <i>C</i>_max 60.2 ± 5.6 ng/mL on day 13 and persisting for up to 140 days. The metabolite-to-parent AUC_0–<i>t</i> ratio (6.2) and the protracted terminal phase are consistent with flip-flop kinetics, where systemic persistence is governed by slow release from the dermal/sebaceous reservoir rather than metabolic clearance. Fipronil desulfinyl was sporadically detected at low levels, confirming that in vivo photodegradation occurs on the animal's surface. These findings consolidate fipronil sulfone as the most reliable marker residue for food safety assessments. Furthermore, the sporadic detection of fipronil desulfinyl confirms that in vivo photodegradation occurs under field conditions, warranting further investigation regarding its contribution to residue dynamics in cattle.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 5","pages":"515-524"},"PeriodicalIF":1.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948764","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":"Pharmacokinetics of a Single Subcutaneous Extended-Release Buprenorphine (Ethiqa XR) in Healthy Beagles","authors":"Kornelia Tiffinger,&nbsp;Hiroko Enomoto,&nbsp;Ronald E. Baynes,&nbsp;Laura M. Neumann,&nbsp;B. Duncan X. Lascelles,&nbsp;Masataka Enomoto","doi":"10.1111/jvp.70082","DOIUrl":"10.1111/jvp.70082","url":null,"abstract":"<p>This study evaluated the pharmacokinetics of an extended-release buprenorphine formulation (Ethiqa XR) in dogs and explored potential sex differences. Twelve healthy intact beagles (6 males and 6 females) received a single subcutaneous injection of Ethiqa XR (0.2 mg/kg). Blood samples were collected up to 168 h post-administration, and plasma buprenorphine concentrations were measured using liquid chromatography–tandem mass spectrometry. Vital signs, sedation, and nausea scores were recorded. Therapeutic plasma concentrations were sustained for approximately 60–90 h in both sexes, depending on the therapeutic threshold used (0.6 or 1.0 ng/mL). Although no significant differences in pharmacokinetics were detected, drug exposure and elimination were greater in females: median peak plasma buprenorphine concentrations (male: 1.6 ng/mL, female: 2.9 ng/mL); median terminal half-life (male: 36.6 h, female: 24.7 h); area under the curve (AUC 0–12 h) (male: 12.8 h*ng/mL, female: 16.9 h*ng/mL); AUC (0–96 h) (male: 94.4 h*ng/mL, female: 137.7 h*ng/mL). Time to maximum concentrations were 24 h in both sexes. Higher buprenorphine concentrations were associated with decreased body temperature and heart rate in both sexes and positively correlated with nausea and sedation scores, but only in females. Ethiqa XR administration resulted in therapeutic plasma concentrations up to 90 h, suggesting it may be an alternative option for post-operative pain control.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 5","pages":"471-486"},"PeriodicalIF":1.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973515","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":"Comparative Pharmacokinetics of Gentamicin in Healthy Young-Adult and Geriatric Horses","authors":"Michelle L. Ceresia,&nbsp;Daniela Bedenice,&nbsp;Andrew Gestrich,&nbsp;Caroline A. McKinney-Aguirre,&nbsp;Mary Rose Paradis,&nbsp;Iman Zaghloul","doi":"10.1111/jvp.70087","DOIUrl":"10.1111/jvp.70087","url":null,"abstract":"<div>\u0000 \u0000 <p>Aging may modify the pharmacokinetic disposition and excretion of gentamicin, although drug dose adjustments in aged horses are uncommon in clinical practice. Since high-dose, once daily dosing of gentamicin is considered therapeutically most effective, a comparative single-dose study was conducted to evaluate the differences in pharmacokinetics between healthy young-adult (5–10 years) and geriatric (≥ 25 years) horses receiving 6.6 mg/kg gentamicin intravenously. Blood samples were collected at designated time-points following drug administration and frozen at −80°C until assayed by a validated immunoassay. Gentamicin plasma concentrations versus time plots were analyzed by noncompartmental analysis using commercial software (WinNonlin-v8.4). Baseline physical examination and hematological parameters did not differ between age groups, except for a lower mean bodyweight in the geriatric group (477 ± 4 kg vs. 402 ± 6 kg). None of the pharmacokinetic parameters were statistically different between age groups. The oldest geriatric horse (41 years) had a longer half-life and lower clearance of 5.3 h and 22.79 L/h, respectively, compared to a range of 1.39–2.56 h and 26.39–40.59 L/h for the remainder of the geriatric group (25–29 years). Further studies may be indicated in horses &gt; 30 years old to determine if dose reduction is necessary in this population.</p>\u0000 </div>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 5","pages":"497-503"},"PeriodicalIF":1.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251887","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 Orally Administered Clonidine in Dogs","authors":"Kevin Pflaum,&nbsp;Julia Albright,&nbsp;Sherry Cox,&nbsp;Joe Smith","doi":"10.1111/jvp.70092","DOIUrl":"10.1111/jvp.70092","url":null,"abstract":"<p>Clonidine is an α-2 agonist shown to be both well tolerated and useful in the treatment of canine fear-based disorders, although it is perceived to have a short duration of action. Clonidine is available in regular release and extended-release formulations, but canine pharmacokinetic (PK) and pharmacodynamic (PD) data on any clonidine formulation are lacking. The aim of this study was to establish PK and PD parameters of regular release (RR) clonidine in dogs. Clonidine RR (<i>n</i> = 6) was orally administered at 0.05 mg/kg to laboratory beagles. Clonidine RR showed a maximum concentration (<i>C</i>_max) 1.5–2 h after administration and declined to below the level of quantification over 4–8 h after administration with an elimination half-life (<i>T</i>_1/2) of 0.65 h. Slight reductions in heart rate and increases in sedation scores were seen in all treatment groups. In conclusion, obtained data indicated a single dose of clonidine RR at 0.05 mg/kg was well tolerated with mild sedation and bradycardia and no other adverse effects in healthy dogs.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 5","pages":"450-456"},"PeriodicalIF":1.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308746","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":"What Do We Know About Cyclooxygenases Expression in the Lower Urinary Tract of Dogs and Cats? A Systematic Review","authors":"Reiner Silveira de Moraes,&nbsp;Luíz Guilherme Dércore Benevenuto,&nbsp;Ana Giulia Gabriel da Rocha Cesario,&nbsp;Julia Franco Ferreira,&nbsp;Suellen Rodrigues Maia,&nbsp;Doughlas Regalin,&nbsp;Dirceu Guilherme de Souza Ramos,&nbsp;Alessandra Melchert,&nbsp;Priscylla Tatiana Chalfun Guimarães-Okamoto","doi":"10.1111/jvp.70090","DOIUrl":"10.1111/jvp.70090","url":null,"abstract":"<p>Cyclooxygenases (COX-1 and COX-2) are key enzymes in the biosynthesis of prostanoids, which mediate physiological functions, inflammation, and the process of carcinogenesis. In dogs and cats, lower urinary tract diseases are prevalent and often complex, requiring targeted therapeutic interventions. Although the role of cyclooxygenases is well established in humans, their expression profile in dogs and cats remains underexplored. This systematic review aimed to consolidate the available knowledge regarding the expression of COX-1 and COX-2 in the lower urinary tract tissues of dogs and cats, highlighting pathological implications and gaps in the literature. A total of 28 original studies were included in this review, which employed methodologies such as immunohistochemistry (IHC), Western blotting (WB), in situ hybridization (ISH), RNA sequencing, and ELISA. The urinary bladder was the most frequently analyzed tissue, followed by the urethra. COX-2 expression was predominantly elevated in tissues with inflammation or neoplasia, whereas COX-1 exhibited a constitutive expression pattern in normal tissues. In cats with feline idiopathic cystitis (FIC), COX-2 expression was significantly elevated in the urethral mucosa. In cases of transitional cell carcinoma (TCC), COX-2 expression varied substantially. The consistent expression of COX-1 in both normal and altered tissues suggested a homeostatic role. Despite the potential of COX-2 as a therapeutic target and prognostic marker, methodological heterogeneity, small sample sizes, and the lack of standardized criteria limit the comparability of findings. This review underscores the need for well-designed studies and standardized approaches to better understand the role of COX enzymes in the uropathology of small animals.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 5","pages":"433-443"},"PeriodicalIF":1.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368818","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":"Characterization of the Pharmacokinetics and Physiological Effects of Tapentadol in Horses","authors":"Annabella D. Lynch,&nbsp;Khursheed R. Mama,&nbsp;Dan S. McKemie,&nbsp;Phillip H. Kass,&nbsp;Heather K. Knych","doi":"10.1111/jvp.70089","DOIUrl":"10.1111/jvp.70089","url":null,"abstract":"<p>Tapentadol is a dual mechanism analgesic utilizing both μ-opioid receptor (MOR) agonism and norepinephrine reuptake inhibition (NRI). This study evaluated the pharmacokinetics and pharmacodynamics of tapentadol as a potential analgesic with the goal of treating pain in horses. Pharmacokinetics of both tapentadol and tapentadol-O-glucuronide were elucidated. Six horses received three separate escalating single oral doses (1, 3, and 5 mg/kg) and a single intravenous (0.32 mg/kg) dose of tapentadol in a four-period sequential design. Concentrations of tapentadol and tapentadol-O-glucuronide were determined using liquid chromatography–tandem mass spectrometry. The maximum concentrations (mean ± SD) in plasma following administration of 1, 3, 5 mg/kg oral tapentadol were 7.98 ± 6.95, 39.8 ± 53.8, and 210.6 ± 234.4 ng/mL at 0.75, 0.63, and 0.38 h, respectively. Maximum plasma concentration (mean ± SD) after a single 0.32 mg/kg IV dose was 339.2 ± 83.5 ng/mL. The maximum concentrations of tapentadol-O-glucuronide following single 1, 3, and 5 mg/kg oral doses and a single 0.32 mg/kg IV dose of tapentadol were 532.6 ± 171.4, 1169.4 ± 345.4, 1559.5 ± 574.6, and 226.4 ± 51.5 ng/mL at times 6.0, 6.0, 7.0, and 0.5 h. Tapentadol was well-tolerated at all doses.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 5","pages":"504-514"},"PeriodicalIF":1.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283907","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}