Journal of veterinary pharmacology and therapeutics最新文献

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Residue Kinetics and Dietary Risk Assessment of Diazepam and Its Metabolites in Grass Carp (Ctenopharyngodon idella): Implications for Aquaculture Safety. 地西泮及其代谢物在草鱼中的残留动力学和饲料风险评估:对养殖安全的影响。
IF 1.4 4区 农林科学
Journal of veterinary pharmacology and therapeutics Pub Date : 2026-07-17 DOI: 10.1111/jvp.70097
Qi Shan, Feng Xu, Mingyuan Wu, Hao Zhou, Huiqing Mei, Jiawei Lin, Lisha Ma, Lichun Li, Shugui Liu, Xuliang Zhai, Yi Yin
{"title":"Residue Kinetics and Dietary Risk Assessment of Diazepam and Its Metabolites in Grass Carp (Ctenopharyngodon idella): Implications for Aquaculture Safety.","authors":"Qi Shan, Feng Xu, Mingyuan Wu, Hao Zhou, Huiqing Mei, Jiawei Lin, Lisha Ma, Lichun Li, Shugui Liu, Xuliang Zhai, Yi Yin","doi":"10.1111/jvp.70097","DOIUrl":"https://doi.org/10.1111/jvp.70097","url":null,"abstract":"<p><p>Diazepam (DZP), a benzodiazepine sedative, has been increasingly detected in various aquatic products including fish, shrimp, and crab in recent surveillance studies, raising public health concerns. This study systematically investigates the residue behavior, metabolite profile, and dietary risk of DZP in grass carp (Ctenopharyngodon idella) following oral administration at a dose of 500 μg/kg body weight. Concentrations of DZP and its metabolites in plasma and tissues were determined using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the drug concentration-time data were fitted using a non-compartmental model embedded in WinNonLin 6.1 pharmacokinetic software. The results indicate that DZP exhibits prolonged elimination kinetics, with tissue elimination half-lives (T<sub>1/2λz</sub>) ranging from 309.44 to 509.75 h, and residues in skin-on muscle did not fall below the limit of quantification until 98 days. Metabolite analysis identified nordiazepam as the primary metabolite, with its concentration surpassing that of the parent compound by Day 21 post-administration, establishing it as a reliable residue marker for DZP in grass carp. The peak human health risk index (HRI) value was 0.392 on Day 4, remaining above the alert threshold (HRI ≥ 0.1) for 21 days, though all values remained below the safety limit (HRI < 1). These findings provide critical data to support the regulation of aquaculture practices and the assessment of dietary exposure risks associated with DZP-contaminated aquatic products.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471287","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}
引用次数: 0
Pharmacokinetics of Bexagliflozin After Intravenous and Oral Administration in Cats 贝沙列净在猫体内静脉和口服的药代动力学。
IF 1.4 4区 农林科学
Journal of veterinary pharmacology and therapeutics Pub Date : 2026-07-15 Epub Date: 2026-04-11 DOI: 10.1111/jvp.70072
Yogini Patel, Sheeva Bhattarai, Céline E. Toutain
{"title":"Pharmacokinetics of Bexagliflozin After Intravenous and Oral Administration in Cats","authors":"Yogini Patel,&nbsp;Sheeva Bhattarai,&nbsp;Céline E. Toutain","doi":"10.1111/jvp.70072","DOIUrl":"10.1111/jvp.70072","url":null,"abstract":"<p>Bexagliflozin, a selective sodium–glucose cotransporter 2 (SGLT2) inhibitor, has been developed for feline diabetes mellitus. This study characterized bexagliflozin pharmacokinetics in healthy cats after single intravenous and oral administrations. Sixteen adult cats received a 1 mg/kg intravenous solution and a 15 mg oral tablet (Bexacat) in a two-period study under fasted conditions. Serial plasma samples were collected up to 72 h and analyzed by a validated LC–MS/MS method (calibration range 1–2000 ng/mL). Pharmacokinetic parameters were derived by non-compartmental analysis. Following intravenous dosing, bexagliflozin showed a low plasma clearance of 348 mL/h/kg. The volumes of distribution during the terminal phase (<i>V</i><sub>z</sub>) and at steady-state (<i>V</i><sub>SS</sub>) were 3.5 and 1.7 L/kg, respectively. The terminal half-life was 7.0 h. After oral dosing of the tablet, absorption was rapid (median <i>T</i><sub>max</sub> 1 h; range 0.5–4 h), with <i>C</i><sub>max</sub> of 1780 ng/mL and a terminal half-life of 6.9 h. Absolute bioavailability was 78% (90% confidence interval: 73%–83%). Exposure was comparable between males and females after both routes (AUC ratios ~97%–103%). Treatments were well tolerated. These pharmacokinetic data indicate bexagliflozin exhibits rapid absorption, high oral bioavailability, and a half-life compatible with once-daily dosing in cats.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 4","pages":"353-360"},"PeriodicalIF":1.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662889","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}
引用次数: 0
Effects of Oral Single-Dose Empagliflozin on Urinary Glucose, Serum β-Hydroxybutyrate, and Plasma Empagliflozin Concentrations in Healthy Adult Dogs 口服单剂量恩格列净对健康成年犬尿糖、血清β-羟基丁酸和血浆恩格列净浓度的影响。
IF 1.4 4区 农林科学
Journal of veterinary pharmacology and therapeutics Pub Date : 2026-07-15 Epub Date: 2026-03-19 DOI: 10.1111/jvp.70066
Andrea D. Plá Gutierrez, M. Lynne O'Sullivan, Etienne Côté, Sandra McConkey, Butch KuKanich, Stephanie E. Martinez
{"title":"Effects of Oral Single-Dose Empagliflozin on Urinary Glucose, Serum β-Hydroxybutyrate, and Plasma Empagliflozin Concentrations in Healthy Adult Dogs","authors":"Andrea D. Plá Gutierrez,&nbsp;M. Lynne O'Sullivan,&nbsp;Etienne Côté,&nbsp;Sandra McConkey,&nbsp;Butch KuKanich,&nbsp;Stephanie E. Martinez","doi":"10.1111/jvp.70066","DOIUrl":"10.1111/jvp.70066","url":null,"abstract":"<p>Empagliflozin is a sodium-glucose cotransporter-2 inhibitor used for treating humans with heart failure, among other conditions. This drug could have applications in veterinary cardiology, but whether empagliflozin has biological effects in dogs when administered at dosages approximating human therapeutic dosages is unknown. This study investigated whether empagliflozin (target dosage, 0.3 mg/kg) could produce significant increases in urinary glucose concentrations and measurable plasma drug concentrations, without increasing serum β-hydroxybutyrate (β-HA) concentrations in dogs. Six healthy, privately-owned dogs weighing 22–36 kg were studied prospectively. Urinary glucose, serum β-HA, and plasma empagliflozin concentrations were measured 0 h, 6 h, 12 h, 24 h, 48 h, and 72 h after single-dose oral administration of 10 mg empagliflozin. The dosage administered was 0.28–0.45 mg/kg. Mean urinary glucose concentration peaked at 24 h (8,041 mg/dL) before returning to baseline (&lt; 40 mg/dL) at 72 h (<i>p</i> &lt; 0.001). Serum β-HA concentrations remained within the reference interval for dogs (&lt; 2.1 mg/dL). Plasma drug concentrations at 24 h were 13 times greater than the reported human in vitro IC50. The half-life was 4.4–6 h. Oral empagliflozin 0.28–0.45 mg/kg produced glucosuria and measurable plasma drug concentrations in healthy dogs, without ketonemia, after a single dose.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 4","pages":"427-432"},"PeriodicalIF":1.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486414","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}
引用次数: 0
Pharmacokinetics of 2 mg/kg Bupivacaine in a Rectus Abdominis Sheath Block in Horses 2mg /kg布比卡因在马腹直肌鞘阻滞中的药代动力学。
IF 1.4 4区 农林科学
Journal of veterinary pharmacology and therapeutics Pub Date : 2026-07-15 Epub Date: 2026-04-01 DOI: 10.1111/jvp.70071
Daniel M. Sakai, Yushun Ishikawa, Jessica S. Y. Im, Shufan Zhang, Rachel A. Reed, Jane E. Quandt, Michele Barletta, Heather K. Knych
{"title":"Pharmacokinetics of 2 mg/kg Bupivacaine in a Rectus Abdominis Sheath Block in Horses","authors":"Daniel M. Sakai,&nbsp;Yushun Ishikawa,&nbsp;Jessica S. Y. Im,&nbsp;Shufan Zhang,&nbsp;Rachel A. Reed,&nbsp;Jane E. Quandt,&nbsp;Michele Barletta,&nbsp;Heather K. Knych","doi":"10.1111/jvp.70071","DOIUrl":"10.1111/jvp.70071","url":null,"abstract":"<p>Administering large volumes of bupivacaine in the rectus abdominis sheath (RAS) block in horses could cause local anesthetic toxicity. This study aimed to evaluate the pharmacokinetics of 2 mg/kg bupivacaine in RAS blocks and the associated toxicity risk. Six healthy adult horses were sedated with xylazine and received an ultrasound-guided bilateral 2-point RAS block. Plasma samples were collected at baseline and from 5 min to 24 h after the block and analyzed using liquid chromatography–tandem mass spectrometry. A noncompartmental analysis was performed to determine the maximum concentration (<i>C</i><sub>max</sub>), the time to reach <i>C</i><sub>max</sub> (<i>T</i><sub>max</sub>), the terminal half-life, the area under the plasma concentration-time curve extrapolated to infinity (AUC<sub>infinity</sub>), and the percentage of AUC<sub>infinity</sub> extrapolated (AUC<sub>extrapolated</sub>). The bupivacaine <i>C</i><sub>max</sub> ranged from 38.4 to 151.8 ng/mL, <i>T</i><sub>max</sub> from 1.5 to 4 h, and the terminal half-life from 9.2 to 46 h. AUC<sub>infinity</sub> ranged from 1351.9 to 2463.3 h·ng/mL, and AUC<sub>extrapolated</sub> ranged from 8.6% to 61.4%. One sample showed plasma levels consistent with neurotoxicity in humans, but was deemed an outlier. The 24-h sampling period was considered insufficient for accurate determination of AUC<sub>infinity</sub> and terminal half-life. Further research on RAS block safety in anesthetized horses is needed before use in colic surgeries.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 4","pages":"402-408"},"PeriodicalIF":1.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592988","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}
引用次数: 0
Pharmacokinetics of Intramuscular and Intravenous Glycopyrrolate in Juvenile New Zealand White Rabbits 甘替罗酯在幼年新西兰大白兔肌内和静脉注射的药代动力学。
IF 1.4 4区 农林科学
Journal of veterinary pharmacology and therapeutics Pub Date : 2026-07-15 Epub Date: 2026-02-25 DOI: 10.1111/jvp.70061
Jocelyn Marchiori, Andrea Sanchez, Kristen Messenger, Jennifer M. Reinhart, Hugues Beaufrère, Sonja Fonfara, Alexander Valverde, Yu Gu, Ron Johnson
{"title":"Pharmacokinetics of Intramuscular and Intravenous Glycopyrrolate in Juvenile New Zealand White Rabbits","authors":"Jocelyn Marchiori,&nbsp;Andrea Sanchez,&nbsp;Kristen Messenger,&nbsp;Jennifer M. Reinhart,&nbsp;Hugues Beaufrère,&nbsp;Sonja Fonfara,&nbsp;Alexander Valverde,&nbsp;Yu Gu,&nbsp;Ron Johnson","doi":"10.1111/jvp.70061","DOIUrl":"10.1111/jvp.70061","url":null,"abstract":"<p>Glycopyrrolate is an alternative to atropine to treat bradyarrhythmias in anesthetized rabbits; however, there are no pharmacokinetic studies in the literature. Six female New Zealand White rabbits received glycopyrrolate 0.05 mg/kg intravenously (IV) in the cephalic vein or intramuscularly (IM) in a complete crossover design. Blood was collected via jugular catheter to determine glycopyrrolate concentrations at baseline, 3, 5, 10, 20, 30, 45, 60 min and 2, 4, 6, 8, 12 and 24 h post-administration. Quantification of plasma glycopyrrolate was performed using liquid chromatography–tandem mass spectrometry. Non-compartmental analysis showed fast clearance (104.03 ± 45.55 mL/kg/min), volume of distribution at steady state of 0.75 ± 0.54 L/kg and terminal half-life of 2.49 ± 1.1 h after IV administration. Terminal half-life was 3.34 ± 1.10 h, T<sub>max</sub> was 0.07 ± 0.01 h, and C<sub>max</sub> was 2.96 ± 2 ng/mL for the IM route. Absolute bioavailability for the IM route was 10.07% ± 3.39%, suggesting higher doses may be needed for this route of administration. This study reports the pharmacokinetic parameters of glycopyrrolate in rabbits after IV and IM administration and may help design future evidence-based administration protocols in this species.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 4","pages":"421-426"},"PeriodicalIF":1.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147307341","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}
引用次数: 0
The Pharmacokinetics of Intravenous and Subcutaneous Ondansetron in Female Beagle Dogs 静脉注射和皮下注射昂丹司琼在雌性比格犬体内的药代动力学。
IF 1.4 4区 农林科学
Journal of veterinary pharmacology and therapeutics Pub Date : 2026-07-15 Epub Date: 2026-02-16 DOI: 10.1111/jvp.70058
Elena D. Landau, Kendal R. Boege, Kristen Messenger, Gregory Ballash, Daniel Gustafson, Carolina Ricco Pereira, Krista Banks, Turi Aarnes, Phillip Lerche, Monica Midon, Kirk A. Muñoz
{"title":"The Pharmacokinetics of Intravenous and Subcutaneous Ondansetron in Female Beagle Dogs","authors":"Elena D. Landau,&nbsp;Kendal R. Boege,&nbsp;Kristen Messenger,&nbsp;Gregory Ballash,&nbsp;Daniel Gustafson,&nbsp;Carolina Ricco Pereira,&nbsp;Krista Banks,&nbsp;Turi Aarnes,&nbsp;Phillip Lerche,&nbsp;Monica Midon,&nbsp;Kirk A. Muñoz","doi":"10.1111/jvp.70058","DOIUrl":"10.1111/jvp.70058","url":null,"abstract":"<p>The purpose of this study was to evaluate the pharmacokinetic profile of ondansetron following intravenous (IV) and subcutaneous (SC) administration in five healthy adult female Beagles. Dogs were administered ondansetron at 0.5 mg/kg IV and SC in a randomized crossover design. On day 0 ondansetron was administered either IV (OV group) or SC (OS group), and 7 days later administered via the opposite route. Plasma samples were collected, and heart and respiratory rates, and rectal temperature were recorded over an 8 h period. Ondansetron concentrations were quantified using liquid chromatography–tandem mass spectrometry. Non-compartmental analysis was performed using commercially available software. Median (min—max) peak plasma concentration following OS was 84.6 (56.0–326.1) ng/mL, which occurred at the first sampled time point of 0.25 (0.25–0.5) h. The terminal half-life was longer in the OS versus the OV group. Bioavailability of ondansetron in the OS group was 84.6 (51.2–132.6)%. Ondansetron administered SC at 0.5 mg/kg to adult healthy dogs has a similar bioavailability and a longer duration of action compared to the IV route of administration. Future pharmacokinetic and pharmacodynamic clinical studies should be performed in dogs utilizing the SC route of administration of ondansetron.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 4","pages":"361-366"},"PeriodicalIF":1.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201811","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}
引用次数: 0
Pharmacokinetics of Long-Acting Ampicillin and Its Impact on the Gut Microbiome and Resistome in Rhesus Macaques (Macaca mulatta) 长效氨苄西林在恒河猴体内的药动学及其对肠道微生物和抵抗组的影响
IF 1.4 4区 农林科学
Journal of veterinary pharmacology and therapeutics Pub Date : 2026-07-15 Epub Date: 2026-02-22 DOI: 10.1111/jvp.70055
Annemiek Maaskant, Ingeborg M. van Geijlswijk, Mathias Devreese, Marc Cherlet, Leo F. van Geest, Jaap A. Wagenaar, Jan A. M. Langermans, Aldert L. Zomer, Jaco Bakker, Ronette Gehring
{"title":"Pharmacokinetics of Long-Acting Ampicillin and Its Impact on the Gut Microbiome and Resistome in Rhesus Macaques (Macaca mulatta)","authors":"Annemiek Maaskant,&nbsp;Ingeborg M. van Geijlswijk,&nbsp;Mathias Devreese,&nbsp;Marc Cherlet,&nbsp;Leo F. van Geest,&nbsp;Jaap A. Wagenaar,&nbsp;Jan A. M. Langermans,&nbsp;Aldert L. Zomer,&nbsp;Jaco Bakker,&nbsp;Ronette Gehring","doi":"10.1111/jvp.70055","DOIUrl":"10.1111/jvp.70055","url":null,"abstract":"<p>Injectable antimicrobials with documented prolonged dosing intervals (&gt; 48 h) for use in rhesus macaques are sparse. The objective of our study was to assess the pharmacokinetics, urine excretion, and effects on gut microbiome and resistome of intramuscular administered long-acting formulation of ampicillin (Albipen LA) in macaques. Four female rhesus macaques (<i>Macaca mulatta</i>) were administered intramuscularly 25 mg/kg anhydrous ampicillin (AMP-LA). Serial plasma samples were collected over a 72 h period and urine samples were collected over a 150 h period. Rectal swabs were collected over a 180-day period for microbiome and resistome analysis. Both plasma and urine samples were analyzed with ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). The pharmacokinetic parameters for AMP-LA ranged as follows: <i>C</i><sub>max</sub> 1.3–10.3 μg/mL, T<sub>1/2</sub> 5.5–10.6 h, AUC<sub>0-∞</sub> 52.5–135.4 μg h/mL. Post-administration, alpha diversity significantly decreased on Day 2 and maintained reduced up till Day 14. Sequence depth of beta-lactam resistance genes significantly increased on Day 2 after administration and then declined until Day 90. A dose of 25 mg/kg AMP-LA administered intramuscularly maintains a plasma concentration ≥ 0.25 μg/mL for up to 48 h. Therefore, administration of AMP-LA could be an effective treatment with a prolonged treatment interval for relevant organisms with short lasting effects on the intestinal microbiome and resistome.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 4","pages":"409-420"},"PeriodicalIF":1.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271492","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}
引用次数: 0
Proposed Meropenem Breakpoints for Interpretation of Antimicrobial Susceptibility Testing of Bacteria Isolated From Dogs 犬类分离细菌药敏试验中美罗培南断点的解释
IF 1.4 4区 农林科学
Journal of veterinary pharmacology and therapeutics Pub Date : 2026-07-15 Epub Date: 2026-03-17 DOI: 10.1111/jvp.70067
Mark G. Papich, Marilyn N. Martinez
{"title":"Proposed Meropenem Breakpoints for Interpretation of Antimicrobial Susceptibility Testing of Bacteria Isolated From Dogs","authors":"Mark G. Papich,&nbsp;Marilyn N. Martinez","doi":"10.1111/jvp.70067","DOIUrl":"10.1111/jvp.70067","url":null,"abstract":"<p>Meropenem is a carbapenem antibiotic used infrequently in veterinary medicine. However, antimicrobial susceptibility testing standards are needed to monitor for resistance caused by carbapenem resistant Enterobacterales (CRE). The Clinical and Laboratory Standards Institute (CLSI) does not have veterinary-specific carbapenem breakpoints for testing bacteria isolated from animals. Our objective was to correct this deficiency and propose clinical antimicrobial susceptibility testing breakpoints for consideration by clinical laboratories, standard-setting organizations, and for monitoring and surveillance programs. We collected pharmacokinetic data from published studies, which were entered into a forecasting program to perform 10,000 Monte Carlo Simulation using a range of dosages considered for administration of meropenem to dogs. Our target for the simulations was a 90% Probability of Target Attainment (PTA) to reach a time-above-MIC for the unbound fraction of the drug (<i>f</i> T &gt; MIC) for at least 40% of the dosing interval. Our results showed that this target can be met for a MIC of ≤ 1 μg/mL (Enterobacterales) with a dose of 20–30 mg/kg IV every 8 h or 10 mg/kg every 6 h. For a one-step higher dilution of ≤ 2 μg/mL (<i>Pseudomonas aeruginosa</i>), a dose of 20–30 mg/kg every 6 h is needed. Therefore, we propose new clinical MIC breakpoints for antimicrobial susceptibility testing these bacteria isolated from dogs of ≤ 1, 2, and ≥ 4 μg/mL for the Susceptible, Intermediate, and Resistant category, respectively, for testing bacteria of the Enterobacterales, and values of ≤ 2, 4, and ≥ 8 μg/mL, respectively, for testing <i>P. aeruginosa</i>.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 4","pages":"367-377"},"PeriodicalIF":1.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474116","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}
引用次数: 0
Ocular Pharmacokinetics of Topical Chloramphenicol in Dogs: Effects of Concentration and Vehicle Formulation 外用氯霉素在狗体内的眼药动学:浓度和载体配方的影响。
IF 1.4 4区 农林科学
Journal of veterinary pharmacology and therapeutics Pub Date : 2026-07-15 Epub Date: 2026-03-24 DOI: 10.1111/jvp.70069
Bar Fruchter, Oren Pe'er, Shir Gonen, Lionel Sebbag
{"title":"Ocular Pharmacokinetics of Topical Chloramphenicol in Dogs: Effects of Concentration and Vehicle Formulation","authors":"Bar Fruchter,&nbsp;Oren Pe'er,&nbsp;Shir Gonen,&nbsp;Lionel Sebbag","doi":"10.1111/jvp.70069","DOIUrl":"10.1111/jvp.70069","url":null,"abstract":"<p>This study compared tear film exposure and retention of four chloramphenicol ophthalmic formulations in dogs, evaluating the effects of drug concentration (0.2% to 5%) and vehicle type (solution vs. ointment). Eight healthy dogs were enrolled in a randomized paired-eye crossover study consisting of two sessions with a 7-day washout. Tear samples were collected via microcapillary tubes at intervals up to 480 min post-instillation, and concentrations were quantified using UV–Vis spectrophotometry. Results showed that chloramphenicol exposure was significantly enhanced by higher concentrations and ointment vehicles. The 0.8% solution achieved a 2.2-fold increase in AUC<sub>0–480</sub> over the 0.2% solution, while the 5% ointment provided a 3.0-fold increase over the 1% ointment. Tear concentration at 480 min was superior for ointments, with the 5% formulation maintaining 88.7 ± 6.8 μg/mL, whereas both solutions fell below quantification limits by the end of the interval. Overall exposure did not differ significantly between the 0.8% solution and 1% ointment. In conclusion, chloramphenicol exposure on the ocular surface depends on both concentration and formulation. High-concentration ointments maximize exposure and prolong retention, providing a pharmacokinetic framework for optimizing therapy in canine bacterial keratitis.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 4","pages":"378-384"},"PeriodicalIF":1.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513244","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}
引用次数: 0
Plasma and Urinary Elimination Profiles of Medetomidine Metabolites in Horses for the Purpose of Doping and Medication Control 马体内美托咪定代谢物的血浆和尿液消除谱,用于兴奋剂和药物控制。
IF 1.4 4区 农林科学
Journal of veterinary pharmacology and therapeutics Pub Date : 2026-07-15 Epub Date: 2026-03-05 DOI: 10.1111/jvp.70063
Yohei Minamijima, Taisuke Kuroda, Yoshimasa Maeda, Shoichi Narita, Shozo Yamashita, Masayuki Yamada
{"title":"Plasma and Urinary Elimination Profiles of Medetomidine Metabolites in Horses for the Purpose of Doping and Medication Control","authors":"Yohei Minamijima,&nbsp;Taisuke Kuroda,&nbsp;Yoshimasa Maeda,&nbsp;Shoichi Narita,&nbsp;Shozo Yamashita,&nbsp;Masayuki Yamada","doi":"10.1111/jvp.70063","DOIUrl":"10.1111/jvp.70063","url":null,"abstract":"<div>\u0000 \u0000 <p>Medetomidine, an α₂-adrenergic agonist, is widely used as a sedative in horses. While its pharmacological effects are established, limited data exist on elimination of its metabolites, 3′-hydroxy medetomidine (HMD) and 3′-carboxy medetomidine (CMD), which are of regulatory interest. HMD is currently targeted in plasma and urine under International Screening Limits (ISLs) established by the International Federation of Horseracing Authorities (IFHA). In this study, seven Thoroughbreds received 6.3 μg/kg of medetomidine intravenously. Blood and urine were collected for 96 h and analyzed by LC–MS/MS after solid-phase extraction with and without enzymatic hydrolysis. Parent drug was detectable in plasma up to 4 h but absent in urine. HMD was quantifiable in plasma to 48 h and urine to 72 h, while CMD, with a distinct profile, was measurable in plasma to 32 h and urine to 72 h. Based on the ISLs, the detection times (DTs) for both plasma and urine were 48 h. Pharmacokinetic modeling estimated clearance at 2.15 L/h/kg and steady-state distribution volume at 1.90 L/kg. These findings show rapid clearance of medetomidine and extended metabolite excretion. The DT of HMD aligns with loss of pharmacological effect, supporting current ISLs and reinforcing the rationale for targeting HMD, with CMD providing supplementary regulatory insight.</p>\u0000 </div>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"49 4","pages":"385-391"},"PeriodicalIF":1.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366058","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}
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